|
1
|
Gemander N, Kemlin D, Depickère S, Kelkar NS, Sharma S, Pannus P, Waegemans A, Olislagers V, Georges D, Dhondt E, Braga M, Heyndrickx L, Michiels J, Thiriard A, Lemy A, Baudoux T, Vandevenne M, Goossens ME, Matagne A, Desombere I, Ariën KK, Ackerman ME, Le Moine A, Marchant A. COVID-19 vaccine responses are influenced by distinct risk factors in naive and SARS-CoV-2 experienced hemodialysis recipients. Vaccine 2025; 44:126544. [PMID: 39608249 DOI: 10.1016/j.vaccine.2024.126544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/28/2024] [Accepted: 11/17/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Clinical risk factors of deficient immune responses to COVID-19 mRNA vaccination in SARS-CoV-2 naive hemodialysis recipients (HDR) have already been identified. Clinical factors influencing hybrid immunity induced by SARS-CoV-2 infection and vaccination in HDR have not been reported. METHODS A comprehensive analysis of antibody (Ab) and T cell responses to two doses of BNT162b2 mRNA vaccination was performed in 103 HDR, including 75 SARS-CoV-2 naive and 28 experienced patients, and in 106 healthy controls (HC) not undergoing HD, including 40 SARS-CoV-2 naive and 66 experienced subjects. Clinical risk factors associated with lower humoral and cellular immunity were analyzed in SARS-CoV-2 naive and experienced HDR by univariate and multivariate analyses. RESULTS Naive HDR had lower neutralizing and non-neutralizing antibody responses to vaccination than naive HC; lower vaccine responses were correlated with previous transplantation, immunosuppressive treatment, corticosteroid treatment, hypoalbuminemia, older age, hypertension, and negative response to hepatitis B vaccination. In contrast, vaccine responses of SARS-CoV-2 experienced HDR were similar to those of HC and were correlated with time between infection and vaccination and with previous transplantation, but not with the other risk factors associated with lower vaccine responses in naive HDR. CONCLUSION COVID-19 vaccine responses are influenced by distinct risk factors in SARS-CoV-2 naive and experienced HDR. These observations have important implications for the understanding of vaccine-induced immunity and for the management of this vulnerable patient population.
Collapse
Affiliation(s)
- Nicolas Gemander
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium; Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université libre de Bruxelles (ULB), Brussels, Belgium.
| | - Delphine Kemlin
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium; Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Stéphanie Depickère
- Platform for Interventional Studies, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
| | - Natasha S Kelkar
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA
| | - Shilpee Sharma
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| | - Pieter Pannus
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| | - Alexandra Waegemans
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| | - Véronique Olislagers
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| | - Daphnée Georges
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium; Laboratory of Enzymology and Protein Folding, Centre for Protein Engineering, InBioS, University of Liège, Liège, Belgium
| | - Emilie Dhondt
- Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
| | - Margarida Braga
- Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
| | - Leo Heyndrickx
- Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
| | - Johan Michiels
- Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium
| | - Anaïs Thiriard
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| | - Anne Lemy
- Department of Nephrology, Marie Curie Hospital, Charleroi, Belgium
| | - Thomas Baudoux
- Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Marylène Vandevenne
- Laboratory of Enzymology and Protein Folding, Centre for Protein Engineering, InBioS, University of Liège, Liège, Belgium
| | - Maria E Goossens
- Platform for Interventional Studies, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
| | - André Matagne
- Laboratory of Enzymology and Protein Folding, Centre for Protein Engineering, InBioS, University of Liège, Liège, Belgium
| | - Isabelle Desombere
- Laboratory of Immune Response, Scientific Direction Infectious Diseases in Humans, Sciensano, Brussels, Belgium
| | - Kevin K Ariën
- Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Margaret E Ackerman
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH, USA; Thayer School of Engineering, Dartmouth College, Hanover, NH, USA
| | - Alain Le Moine
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium; Department of Nephrology, Dialysis and Transplantation, Erasme Hospital, Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Arnaud Marchant
- European Plotkin Institute for Vaccinology, Université libre de Bruxelles (ULB), Brussels and ULB Centre for Research in Immunology (U-CRI), Université libre de Bruxelles (ULB), Gosselies, Belgium
| |
Collapse
|
|
2
|
Carriazo S, Abasheva D, Duarte D, Ortiz A, Sanchez-Niño MD. SCARF Genes in COVID-19 and Kidney Disease: A Path to Comorbidity-Specific Therapies. Int J Mol Sci 2023; 24:16078. [PMID: 38003268 PMCID: PMC10671056 DOI: 10.3390/ijms242216078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 10/29/2023] [Accepted: 11/06/2023] [Indexed: 11/26/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has killed ~7 million persons worldwide. Chronic kidney disease (CKD) is the most common risk factor for severe COVID-19 and one that most increases the risk of COVID-19-related death. Moreover, CKD increases the risk of acute kidney injury (AKI), and COVID-19 patients with AKI are at an increased risk of death. However, the molecular basis underlying this risk has not been well characterized. CKD patients are at increased risk of death from multiple infections, to which immune deficiency in non-specific host defenses may contribute. However, COVID-19-associated AKI has specific molecular features and CKD modulates the local (kidney) and systemic (lung, aorta) expression of host genes encoding coronavirus-associated receptors and factors (SCARFs), which SARS-CoV-2 hijacks to enter cells and replicate. We review the interaction between kidney disease and COVID-19, including the over 200 host genes that may influence the severity of COVID-19, and provide evidence suggesting that kidney disease may modulate the expression of SCARF genes and other key host genes involved in an effective adaptive defense against coronaviruses. Given the poor response of certain CKD populations (e.g., kidney transplant recipients) to SARS-CoV-2 vaccines and their suboptimal outcomes when infected, we propose a research agenda focusing on CKD to develop the concept of comorbidity-specific targeted therapeutic approaches to SARS-CoV-2 infection or to future coronavirus infections.
Collapse
Affiliation(s)
- Sol Carriazo
- Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON M5G 2C4, Canada;
- RICORS2040, 28049 Madrid, Spain;
| | - Daria Abasheva
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain; (D.A.); (D.D.)
| | - Deborah Duarte
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain; (D.A.); (D.D.)
| | - Alberto Ortiz
- RICORS2040, 28049 Madrid, Spain;
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain; (D.A.); (D.D.)
- Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain
| | - Maria Dolores Sanchez-Niño
- RICORS2040, 28049 Madrid, Spain;
- Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28049 Madrid, Spain; (D.A.); (D.D.)
- Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, Spain
| |
Collapse
|
|
3
|
Girndt M, Houser P, Manllo-Karim R, Ervin JE, Charytan C, Chow S, Symonian-Silver M, Lehrner L, Linfert D, Shemin D, Michelsen A, Xie F, Janssen RS. Long-term immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B) compared with HepB-Eng (Engerix-B) in adults with chronic kidney disease. Vaccine 2023; 41:3224-3232. [PMID: 37085451 DOI: 10.1016/j.vaccine.2023.04.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/04/2023] [Accepted: 04/08/2023] [Indexed: 04/23/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB-CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB-Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB-Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19). METHODS HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10mIU/mL received additional HepB-CpG or HepB-Eng doses. RESULTS 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups. CONCLUSIONS Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. CLINICALTRIALS gov: NCT01282762.
Collapse
Affiliation(s)
- Matthias Girndt
- Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle 06120, Germany
| | - Patricia Houser
- Amherst Family Practice, 1867 Amherst Street, Winchester, VA 22601, USA
| | - Roberto Manllo-Karim
- Gamma Medical Research, Inc., 222 East Ridge Road, Suite 214, Mcallen, TX 78503, USA
| | - John E Ervin
- Center for Pharmaceutical Research, 1010 Carondelet Drive, Suite 426, Kansas City, MO 64114, USA
| | - Chaim Charytan
- New York-Presbyterian Queens, 56-45 Main Street, Flushing, NY 11355, USA
| | - Stephen Chow
- Department of Medicine, Michael Garron Hospital, 825 Coxwell Avenue, Toronto, ON, Canada
| | - Margarita Symonian-Silver
- National Institute of Clinical Research, 1000 Corporate Center Drive, Suite 330, Monterey Park, CA 91754, USA
| | - Lawrence Lehrner
- Kidney Specialists of Southern Nevada, 500 S Rancho Drive, #12, Las Vegas, NV 89106, USA
| | - Douglas Linfert
- Nephrology Associates, 28 White Bridge Pike, Suite 300, Nashville, TN 37205, USA
| | - Douglas Shemin
- Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
| | - Ann Michelsen
- Gemeinschaftspraxis für Innere Medizin, Pferdebachstr. 29, 58455 Witten, Germany
| | - Fang Xie
- Dynavax Technologies Corporation, 2100 Powell Street, Suite 720, Emeryville, CA 94608, USA
| | - Robert S Janssen
- Dynavax Technologies Corporation, 2100 Powell Street, Suite 720, Emeryville, CA 94608, USA.
| |
Collapse
|
|
4
|
Humoral and cellular response after BNT162b2 vaccine booster in hemodialysis patients and kidney transplant recipients. Clin Exp Nephrol 2023; 27:445-453. [PMID: 36795176 PMCID: PMC9933795 DOI: 10.1007/s10157-023-02317-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 01/10/2023] [Indexed: 02/17/2023]
Abstract
BACKGROUND Vulnerable populations, such as hemodialysis (HD) patients and kidney transplant (RTx) recipients, have priority for anti-COVID-19 vaccination, because of their impaired immune status. Here, we investigated the immune response after vaccination with BNT162b2 (two doses plus booster) in HD and RTx patients. METHODS A prospective, observational study was started in two homogeneous groups of 55 HD and 51 RTx patients previously matched from a cohort of 336 patients. Anti-RBD IgG levels, assayed after the second dose with BNT162b2 mRNA, were used to stratify subjects into quintiles. After the second dose and after booster, anti-RBD and IGRA test were evaluated in RTx and HD, belonging to the first and fifth quintiles. RESULTS After the second dose of vaccine, the median circulating levels of anti-RBD IgG were significantly higher in HD (1456 AU/mL) compared to RTx (27.30 AU/mL). IGRA test showed significantly higher values in the HD (382 mIU/mL) compared with the RTx (73 mIU/mL). After the booster, humoral response increased significantly in both HD (p = 0.0002) and RTx groups (p = 0.009), whereas the T-cellular immunity remained essentially stable in most patients. In RTx patients with a low humoral response after the second dose, the third dose did not significantly strengthen either humoral or cellular immunity. CONCLUSIONS For HD and RTx, there is great variability in the humoral response to anti-COVID-19 vaccination, with a stronger response in the HD group. The booster dose was ineffective at reinforcing the humoral and cellular immune response in most RTx patients hyporesponsive to the second dose.
Collapse
|
|
5
|
Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
6
|
Gray LT, Raczy MM, Briquez PS, Marchell TM, Alpar AT, Wallace RP, Volpatti LR, Sasso MS, Cao S, Nguyen M, Mansurov A, Budina E, Watkins EA, Solanki A, Mitrousis N, Reda JW, Yu SS, Tremain AC, Wang R, Nicolaescu V, Furlong K, Dvorkin S, Manicassamy B, Randall G, Wilson DS, Kwissa M, Swartz MA, Hubbell JA. Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant. Biomaterials 2021; 278:121159. [PMID: 34634664 PMCID: PMC8482845 DOI: 10.1016/j.biomaterials.2021.121159] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/20/2021] [Accepted: 09/27/2021] [Indexed: 12/30/2022]
Abstract
The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist. Thus, p(Man-TLR7) is designed to target relevant antigen-presenting cells (APCs) via mannose-binding receptors and then activate TLR7 upon endocytosis. The p(Man-TLR7) construct is amenable to conjugation to protein antigens such as the Spike protein of SARS-CoV-2, yielding Spike-p(Man-TLR7). Here, we demonstrate Spike-p(Man-TLR7) vaccination elicits robust antigen-specific cellular and humoral responses in mice. In adult and elderly wild-type mice, vaccination with Spike-p(Man-TLR7) generates high and long-lasting titers of anti-Spike IgGs, with neutralizing titers exceeding levels in convalescent human serum. Interestingly, adsorbing Spike-p(Man-TLR7) to the depot-forming adjuvant alum amplified the broadly neutralizing humoral responses to levels matching those in mice vaccinated with formulations based off of clinically-approved adjuvants. Additionally, we observed an increase in germinal center B cells, antigen-specific antibody secreting cells, activated T follicular helper cells, and polyfunctional Th1-cytokine producing CD4+ and CD8+ T cells. We conclude that Spike-p(Man-TLR7) is an attractive, next-generation subunit vaccine candidate, capable of inducing durable and robust antibody and T cell responses.
Collapse
Affiliation(s)
- Laura T Gray
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Michal M Raczy
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Priscilla S Briquez
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Tiffany M Marchell
- Committee on Immunology, University of Chicago, Chicago, IL, 60637, United States
| | - Aaron T Alpar
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Rachel P Wallace
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Lisa R Volpatti
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Maria Stella Sasso
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Shijie Cao
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Mindy Nguyen
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Aslan Mansurov
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Erica Budina
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Elyse A Watkins
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Ani Solanki
- Animal Resources Center, University of Chicago, Chicago, IL, 60637, United States
| | - Nikolaos Mitrousis
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Joseph W Reda
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Shann S Yu
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Andrew C Tremain
- Committee on Immunology, University of Chicago, Chicago, IL, 60637, United States
| | - Ruyi Wang
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Vlad Nicolaescu
- Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL, 60637, United States
| | - Kevin Furlong
- Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL, 60637, United States
| | - Steve Dvorkin
- Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL, 60637, United States
| | - Balaji Manicassamy
- Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, 52242, United States
| | - Glenn Randall
- Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL, 60637, United States
| | - D Scott Wilson
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States; Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, 21231, United States
| | - Marcin Kwissa
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States
| | - Melody A Swartz
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States; Committee on Immunology, University of Chicago, Chicago, IL, 60637, United States; Committee on Cancer Biology, University of Chicago, Chicago, IL, 60637, United States; Ben May Department of Cancer Research, University of Chicago, Chicago, IL, 60637, United States.
| | - Jeffrey A Hubbell
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, United States; Committee on Immunology, University of Chicago, Chicago, IL, 60637, United States; Committee on Cancer Biology, University of Chicago, Chicago, IL, 60637, United States.
| |
Collapse
|
|
7
|
Huang R, Gan R, Zhang D, Xiao J. The comparative safety of human papillomavirus vaccines: A Bayesian network meta-analysis. J Med Virol 2021; 94:729-736. [PMID: 34453758 DOI: 10.1002/jmv.27304] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 08/26/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIMS The safety of human papillomavirus (HPV) vaccines, one of the major challenges to public vaccination, has been controversial. This study assessed the adverse reactions of various HPV vaccines, including bivalent HPV (2vHPV), quadrivalent HPV (4vHPV), and 9-valent HPV (9vHPV) vaccines. METHODS PubMed, Embase, and Central databases were searched for randomized controlled trials (RCTs) on the comparative safety of HPV vaccines. A network meta-analysis was performed based on the Bayesian framework random-effects model. RESULTS This study included 23 RCTs. Analysis across these reports indicated that the 2vHPV vaccine was associated with significantly more systemic adverse events than the 4vHPV vaccine (risk ratio [RR]: 1.28, 95% credible interval [CrI]: 1.14-1.44), 9vHPV vaccine (RR: 1.25, 95% CrI: 1.06-1.49), and placebo (RR: 1.31, 95% CrI: 1.18-1.46). However, there were no statistically significant differences in serious adverse events between the vaccinated and placebo groups. For injection-site adverse events, there were substantial inconsistencies between the direct and indirect effects; therefore, the analysis results of the safety were presented only for systemic and serious adverse events. CONCLUSIONS The 2vHPV vaccine resulted in more systemic adverse events than other vaccines and placebo. No significant differences in serious adverse events were observed. Further studies are needed to obtain more information regarding the safety of HPV vaccines.
Collapse
Affiliation(s)
- Rongdong Huang
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
| | - Ruihuan Gan
- Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China
| | - Dongjuan Zhang
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
| | - Jianxiong Xiao
- Center for Vaccine Clinical Research, Fujian Provincial Center for Disease Control and Prevention, Fuzhou, China
| |
Collapse
|
|
8
|
Jahn M, Korth J, Dorsch O, Anastasiou OE, Sorge-Hädicke B, Tyczynski B, Gäckler A, Witzke O, Dittmer U, Dolff S, Wilde B, Kribben A. Humoral Response to SARS-CoV-2-Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis. Vaccines (Basel) 2021; 9:360. [PMID: 33918085 PMCID: PMC8070660 DOI: 10.3390/vaccines9040360] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 04/01/2021] [Accepted: 04/03/2021] [Indexed: 12/19/2022] Open
Abstract
mRNA-based SARS-CoV-2 vaccines offer a preventive strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that is of interest in the care of patients on hemodialysis (HDP). We measured humoral immune responses in 72 HDP after standard vaccination with two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech). Antibody responses were evaluated with an anti-SARS-CoV-2 IgG ChemiLuminescent ImmunoAssay (CLIA) two weeks after the second dose. In addition, SARS-CoV-2 IgG was determined in a control of 16 healthy healthcare workers (HCW). The control group of HCW has shown a strong antibody response with a median (MD (Q1; Q3)) antibody titer of 800.0 AU/mL (520.5; 800.0). In comparison to HCW, HDP under 60 years of age responded equally (597.0 AU/mL (410.5; 800.0), p = 0.051). However, the antibody responses of the HDP negatively correlated with age (r2 = 0.2954 p < 0.0001), leading to significantly lower antibody titers in HDP over 60 years (280.0 AU/mL (45.7; 477.0), p < 0.0001). To thoroughly understand the immunogenicity of the new mRNA-based vaccines in HDP, longitudinal data on the effectiveness and durability of antibody responses are needed. Modifications of immunization schedules should be considered in HDP with low or without antibody responsiveness after standard vaccination to boost immune reactivity and prolong protective effects in these vulnerable patients.
Collapse
Affiliation(s)
- Michael Jahn
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| | - Johannes Korth
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| | - Oliver Dorsch
- KfH Kuratorium für Dialyse und Nierentransplantation e.V, KfH-Nierenzentrum Friesener Straße 37a, 96317 Kronach, Germany;
| | - Olympia Evdoxia Anastasiou
- Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147 Essen, Germany; (O.E.A.); (U.D.)
| | - Burkhard Sorge-Hädicke
- KfH Kuratorium für Dialyse und Nierentransplantation e.V, KfH-Nierenzentrum Alfried-Krupp-Str. 43, 45131 Essen, Germany;
| | - Bartosz Tyczynski
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| | - Anja Gäckler
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| | - Oliver Witzke
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (O.W.); (S.D.)
| | - Ulf Dittmer
- Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147 Essen, Germany; (O.E.A.); (U.D.)
| | - Sebastian Dolff
- Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (O.W.); (S.D.)
| | - Benjamin Wilde
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| | - Andreas Kribben
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany; (J.K.); (B.T.); (A.G.); (B.W.); (A.K.)
| |
Collapse
|
|
9
|
Fabrizi F, Cerutti R, Dixit V, Ridruejo E. Hepatitis B virus vaccine and chronic kidney disease. The advances. Nefrologia 2021; 41:115-122. [PMID: 36165374 DOI: 10.1016/j.nefroe.2020.08.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 08/14/2020] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Hepatitis B is an important agent of liver disease in patients with chronic kidney disease and chronic HBV infection promotes the development of CKD in the adult general population. Patients with CKD have a suboptimal response to various vaccines, and it remains unclear how we boost the immune response of CKD patients to HB vaccine. STUDY AIMS AND DESIGN We performed a narrative review to assess the mechanisms of lower immunogenicity of HBV vaccine in CKD population; multiple approaches to improve the response rate of CKD patients to HBV vaccine have been reported. This is a very important topic for nephrologists who often serve as primary case providers for patients with CKD. RESULTS The recommended vaccine schedule for CKD patients including those on maintenance dialysis is based on recombinant vaccine, four doses (month 0,1,2, and 6; 40mcg each) by intramuscular route (deltoid muscle). According to RCTs or observational studies, some recombinant vaccines with adjuvants (i.e., HBV-AS02 and HBV-AS04) look promising. HBV-AS04 showed to give better seroprotection rates and durable immune response over extended follow-ups compared with licensed HBV vaccine in CKD patients. The seroprotection rate was 95% (97/102) and 82% (202/248) in pre-dialysis and dialysis patients, respectively, one month after completing vaccine schedule with HBV-AS04. HBV-AS02 was superior to licensed vaccine in terms of seroprotection rate, 76.9% vs. 37.6%. CONCLUSIONS We suggest adjuvanted recombinant (HBV-AS04) vaccine (0,1,2 and 3 months; 20 mcg each dose) and post vaccination testing of anti-HBs antibody after vaccination. Booster doses to patients whose anti-HBs titers fall below the seroprotection level (<10IU/mL) during the follow-up are appropriate. The patho-physiologic mechanisms responsible for the poor immunogenicity of HBV vaccine in CKD patients are under active investigation.
Collapse
Affiliation(s)
- Fabrizio Fabrizi
- IRCCS Ca' Granda Foundation and Maggiore Polyclinic Hospital, Milano, Italy.
| | - Roberta Cerutti
- IRCCS Ca' Granda Foundation and Maggiore Polyclinic Hospital, Milano, Italy
| | - Vivek Dixit
- Division of Digestive Diseases, UCLA School of Medicine, CA, USA
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC", Ciudad de Buenos Aires, Argentina; Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Provincia de Buenos Aires, Argentina; Latin American Liver Research, Educational and Awareness Network (LALREAN), Pilar, Provincia de Buenos Aires, Argentina
| |
Collapse
|
|
10
|
Fabrizi F, Cerutti R, Garcia-Agudo R, Bellincioni C, Porata G, Frontini G, Aoufi-Rabih S, Messa P. Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial. Clin Res Hepatol Gastroenterol 2020; 44:905-912. [PMID: 32144074 DOI: 10.1016/j.clinre.2020.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/21/2020] [Accepted: 01/22/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited. AIM We have measured antibody (anti-HBs) persistence for up to 72 months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine. METHODS Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3 month (n=217 patients) and 0,1,2, and 6 month (n=31 patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12 months and then every year up to 72 months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine. RESULTS Two hundred and seventy-two patients were included and 248 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed. CONCLUSIONS Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.
Collapse
Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy.
| | - Roberta Cerutti
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | | | - Cecilia Bellincioni
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | - Giulia Porata
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | - Giulia Frontini
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy
| | | | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Pad. Croff, Via Commenda 15, 20122 Milano, Italy; University School of Medicine, Milan, Italy
| |
Collapse
|
|
11
|
Duszenko N, van Willigen DM, Welling MM, de Korne CM, van Schuijlenburg R, Winkel BM, van Leeuwen FW, Roestenberg M. A Supramolecular Platform Technology for Bacterial Cell Surface Modification. ACS Infect Dis 2020; 6:1734-1744. [PMID: 32364374 PMCID: PMC7359023 DOI: 10.1021/acsinfecdis.9b00523] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
In an era of antimicrobial resistance, a better understanding of the interaction between bacteria and the sentinel immune system is needed to discover new therapeutic targets for combating bacterial infectious disease. Sentinel immune cells such as macrophages phagocytose intact bacteria and thereby initiate ensuing immune responses. The bacterial surface composition is a key element that determines the macrophage signaling. To study the role of the bacterial cell surface composition in immune recognition, we developed a platform technology for altering bacterial surfaces in a controlled manner with versatile chemical scaffolds. We show that these scaffolds are efficiently loaded onto both Gram-positive and -negative bacteria and that their presence does not impair the capacity of monocyte-derived macrophages to phagocytose bacteria and subsequently signal to other components of the immune system. We believe this technology thus presents a useful tool to study the role of bacterial cell surface composition in disease etiology and potentially in novel interventions utilizing intact bacteria for vaccination.
Collapse
Affiliation(s)
- Nikolas Duszenko
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Danny M. van Willigen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Mick M. Welling
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Clarize M. de Korne
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Roos van Schuijlenburg
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Beatrice M.F. Winkel
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| | - Fijs W.B. van Leeuwen
- Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
- Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam 1066 CX, The Netherlands
| | - Meta Roestenberg
- Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
- Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, Leiden 2333 ZA, The Netherlands
| |
Collapse
|
|
12
|
Abstract
PURPOSE OF REVIEW The gradual replacement of inactivated whole cell and live attenuated vaccines with subunit vaccines has generally reduced reactogenicity but in many cases also immunogenicity. Although only used when necessary, adjuvants can be key to vaccine dose/antigen-sparing, broadening immune responses to variable antigens, and enhancing immunogenicity in vulnerable populations with distinct immunity. Licensed vaccines contain an increasing variety of adjuvants, with a growing pipeline of adjuvanted vaccines under development. RECENT FINDINGS Most adjuvants, including Alum, Toll-like receptor agonists and oil-in-water emulsions, activate innate immunity thereby altering the quantity and quality of an adaptive immune response. Adjuvants activate leukocytes, and induce mediators (e.g., cytokines, chemokines, and prostaglandin-E2) some of which are biomarkers for reactogenicity, that is, induction of local/systemic side effects. Although there have been safety concerns regarding a hypothetical risk of adjuvants inducing auto-immunity, such associations have not been established. As immune responses vary by population (e.g., age and sex), adjuvant research now incorporates principles of precision medicine. Innovations in adjuvant research include use of human in vitro models, immuno-engineering, novel delivery systems, and systems biology to identify biomarkers of safety and adjuvanticity. SUMMARY Adjuvants enhance vaccine immunogenicity and can be associated with reactogenicity. Novel multidisciplinary approaches hold promise to accelerate and de-risk targeted adjuvant discovery and development. VIDEO ABSTRACT: http://links.lww.com/MOP/A53.
Collapse
Affiliation(s)
- Etsuro Nanishi
- Precision Vaccines Program
- Division of Infectious Diseases, Boston Children's Hospital
- Harvard Medical School, Boston
| | - David J. Dowling
- Precision Vaccines Program
- Division of Infectious Diseases, Boston Children's Hospital
- Harvard Medical School, Boston
| | - Ofer Levy
- Precision Vaccines Program
- Division of Infectious Diseases, Boston Children's Hospital
- Harvard Medical School, Boston
- Broad Institute of MIT & Harvard, Cambridge, Massachusetts, USA
| |
Collapse
|
|
13
|
Fabrizi F, Cerutti R, Nardelli L, Tripodi F, Messa P. HBV vaccination with Fendrix is effective and safe in pre-dialysis CKD population. Clin Res Hepatol Gastroenterol 2020; 44:49-56. [PMID: 31327620 DOI: 10.1016/j.clinre.2019.06.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/08/2019] [Accepted: 06/20/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with chronic kidney disease have a poor response to hepatitis B vaccine due to the immunodeficiency conferred from chronic uremia. A recombinant HB vaccine containing an improved adjuvant system AS04 (HBV-AS04) has been manufactured but scarce evidence exists on HBV-AS04 use among patients with CKD. AIM To assess efficacy and safety of an adjuvanted recombinant vaccine (HBV-AS04) in a large cohort of CKD patients at pre-dialysis stage (with susceptibility to HBV infection). METHODS Patients were prospectively enrolled to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 1, 2, 3, and 4. Anti-HBs surface antibody concentrations were tested at intervals of 1, 2, 3, 4, and 12months. Multivariate analyses were performed to assess the parameters, which predicted immunologic response to HBV-AS04 vaccine. RESULTS One hundred and seven patients were included and 102 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 95% (97/102) (mean anti-HBs antibody titers, 688.9±385mIU/mL), according to per-protocol analysis. Serum haemoglobin levels were greater in responder than non- or low-responder patients to HBV-AS04 (P=0.04) and this was confirmed by multivariate analysis. The seroprotection rate at month 50 was 88% (30/34) with lower anti-HBs antibody titers (218.5±269.6mIU/mL, P=0.001). No major side effects were observed. CONCLUSIONS Our prospective study performed in a real-world setting showed a high immunogenicity and safety of HBV-AS04 vaccine in patients with CKD not yet on maintenance dialysis. Studies provided with longer follow-ups are under way to assess the durability of seroprotection in responders.
Collapse
Affiliation(s)
| | | | | | | | - Piergiorgio Messa
- Division of Nephrology, Milan, Italy; Maggiore Hospital and IRCCS Foundation, University School of Medicine, Milan, Italy
| |
Collapse
|
|
14
|
Jia S, Li J, Liu Y, Zhu F. Precision immunization: a new trend in human vaccination. Hum Vaccin Immunother 2020; 16:513-522. [PMID: 31545124 DOI: 10.1080/21645515.2019.1670123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Vaccination has been one of the major revolutions in the history of human health. Vaccination programs have targeted entire populations such as infants or elderly subjects as a matter of being efficient with time and resources. These general populations are heterogeneous in terms of factors such as ethnicity, health status, and socio-economics. Thus, there have been variations in the safety and effectiveness profiles of certain vaccinations according to current population-wide strategies. As the concept of precision medicine has been raised in recent years, many researchers have suggested that vaccines could be administered more precisely in terms of particular target populations, vaccine formulations, regimens, and dosage levels. This review addresses the concept and framework of precision immunization, summarizes recent and representative clinical trials of among specific populations, mentions important factors to be addressed in customizing vaccinations, and provides suggestions on the establishment of precision immunization with the goal of maximizing the effectiveness of vaccines in general.
Collapse
Affiliation(s)
- Siyue Jia
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Jingxin Li
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Yuanbao Liu
- Expanded Program on Immunization Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China.,NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| | - Fengcai Zhu
- Vaccine Clinical Evaluation Department, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China.,NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, PR China
| |
Collapse
|
|
15
|
Dimitrov Y, Ducher M, Kribs M, Laurent G, Richter S, Fauvel JP. Variables linked to hepatitis B vaccination success in non-dialyzed chronic kidney disease patients: Use of a bayesian model. Nephrol Ther 2019; 15:215-219. [PMID: 31129001 DOI: 10.1016/j.nephro.2019.02.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 02/01/2019] [Accepted: 02/03/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Hepatitis B vaccination is recommended for chronic kidney disease (CKD) patients before starting dialysis. We performed an analyis aimed to describe the clinical and biological parameters related to the success of vaccination in CKD patients before starting dialysis. METHODS We extracted data of 170 non-dialyzed patients who were offered hepatitis B vaccination from a register. They received a first vaccination of 40μg followed by boosters after one, two and six months. Patients were considered protected if their hepatitis B antibody level was >10IU/L, three months apart. A logistic regression and a Bayesian model were used to describe the relationships between variables and the success of vaccination. RESULTS Vaccination protected 50.6% of the patients. Model adjustment to the data was higher using the Bayesian model compared to the logistic regression (with area under the ROC curve of 0.955±0.007 vs 0.775±0.066 respectively). The Bayesian model's robustness studied using a 10 fold cross validation showed a percentage of misclassified subjects of 12.4±1.8%, a sensitivity of 87.7±0.3%, a specificity of 87.5±0.3%, a positive predictive value of 87.8±0.3% and negative predictive value of 87.4±0.2%. As classified by the Bayesian model, the variables most related to successful vaccination were, in descending order: age, eGFR, protidemia, albuminemia, cause of renal failure, gender, previous vaccination and weight. CONCLUSION The Bayesian network confirmed that both kidney function and nutritional status of patients are important factors to explain the success of vaccination against hepatitis B in CKD patients before dialysis. For research purposes, before an external validation, the network can be used online at www.hed.cc/?s=Bhepatitis&n=ReseauhepatiteBsup10.neta.
Collapse
Affiliation(s)
- Yves Dimitrov
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France.
| | - Michel Ducher
- Pharmacy Department, hospices civils de Lyon, université Claude-Bernard Lyon 1, 69000 Lyon, France
| | - Marc Kribs
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France
| | - Guillaume Laurent
- Nephrology Department, centre hospitalier de Haguenau, 64, avenue du professeur Leriche, 67500 Haguenau, France
| | | | - Jean-Pierre Fauvel
- Hospices civils de Lyon, université Claude-Bernard Lyon 1, 69000 Lyon, France
| |
Collapse
|
|
16
|
Taleghani N, Bozorg A, Azimi A, Zamani H. Immunogenicity of HPV and HBV vaccines: adjuvanticity of synthetic analogs of monophosphoryl lipid A combined with aluminum hydroxide. APMIS 2019; 127:150-157. [PMID: 30746792 DOI: 10.1111/apm.12927] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 12/28/2018] [Indexed: 11/29/2022]
Abstract
Monophosphoryl lipid A (MPL), a purified and detoxified product of lipopolysaccharide (LPS) of Salmonella minnesota R595, has been used as an adjuvant in different vaccines. In this study, the efficacy of human papillomaviruses (HPV) and hepatitis B virus (HBV) vaccines formulated with aluminum hydroxide combined with two different synthetic MPLs, 3D-(6-acyl)-PHAD or 3D-PHAD, or aluminum hydroxide combined with the mixtures of such MPLs, has been assessed. The immunogenicity in female BALB/c mice was verified by two intramuscular injections of differently formulated HPV and HBV vaccines and the total immunoglobulin G (IgG) antibody response was considered to compare the employed adjuvants. As verified experimentally, a mixture of 3D-(6-acyl)-PHAD and 3D-PHAD was able to induce significantly higher antibody titer than that of either 3D-(6-acyl)-PHAD or 3D-PHAD, when used individually. Interestingly, based on the responses achieved in terms of the total antibody levels, such mixture of synthetic MPLs was found to be even more effective than the bacterially derived MPL. Accordingly, the obtained results indicated that, if designed appropriately, synthetic MPL molecules could provide improved adjuvanticity with high level of consistency.
Collapse
Affiliation(s)
- Nastaran Taleghani
- Biotechnology Department, College of Science, University of Tehran, Tehran, Iran
| | - Ali Bozorg
- Biotechnology Department, College of Science, University of Tehran, Tehran, Iran
| | - Amin Azimi
- Biotechnology Department, College of Science, University of Tehran, Tehran, Iran
| | - Homa Zamani
- Department of Cell Therapy and Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| |
Collapse
|
|
17
|
Kosmadakis G, Albaret J, Correia EDC, Somda F, Aguilera D. Vaccination practices in dialysis patients: A narrative review. Semin Dial 2018; 31:507-518. [PMID: 29742283 DOI: 10.1111/sdi.12709] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
In a period of turmoil concerning vaccination practices, there is a serious conflict between scientifically reasonable, evidence-based guidelines and the far-fetched rumors or misconceptions concerning the vaccination practices in the general population. When a significant portion of the medical and paramedical personnel may be deliberately unvaccinated against common biological agents, achieving effective vaccination rates in the dialysis population may be complicated. Vaccination rates are unacceptably low in dialysis patients and seroconversion rates are even lower; further, serological follow-up is generally poor. The particularly anergic immune system of the advanced chronic kidney disease patients is partly a cause of both high rates of infection and low rates of seroconversions. This narrative review is an effort to summarize current knowledge concerning the vaccination practices in dialysis patients with some specific recommendations based on these facts. Of particular interest is a new vaccine, the Zoster Recombinant, Adjuvanted Vaccine (Shingrix), which we will include in our discussion.
Collapse
Affiliation(s)
- Georges Kosmadakis
- Hemodialyis Unit and Pole Metabolique, Centre Hospitalier Jacques Lacarin, Vichy, France
| | - Julie Albaret
- Hemodialyis Unit and Pole Metabolique, Centre Hospitalier Jacques Lacarin, Vichy, France
| | | | - Frederic Somda
- Hemodialyis Unit and Pole Metabolique, Centre Hospitalier Jacques Lacarin, Vichy, France
| | - Didier Aguilera
- Hemodialyis Unit and Pole Metabolique, Centre Hospitalier Jacques Lacarin, Vichy, France
| |
Collapse
|
|
18
|
|
|
19
|
Mulley WR, Le STT, Ives KE. Primary seroresponses to double-dose compared with standard-dose hepatitis B vaccination in patients with chronic kidney disease: a systematic review and meta-analysis. Nephrol Dial Transplant 2017; 32:136-143. [PMID: 26763670 DOI: 10.1093/ndt/gfv443] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 12/07/2015] [Indexed: 01/27/2023] Open
Abstract
Background Clinical guidelines recommend double-dose hepatitis B vaccination for patients requiring dialysis, due to an increased risk of hepatitis B infection and reduced vaccine responsiveness. There are no recommendations for patients with chronic kidney disease (CKD) prior to dialysis. Methods We performed a systematic review and meta-analysis of randomized and quasi-randomized trials comparing efficacy (seroresponses) and harms of double-dose compared with standard-dose hepatitis B vaccination in patients with CKD, including those requiring dialysis. A systematic literature search (CENTRAL, MEDLINE and EMBASE) was performed using a predetermined search strategy. Relative risks were calculated from pooled data using a random-effects model with subgroup analysis by dialysis requirement and vaccine type. Results Seven studies (501 patients) fulfilled review criteria: four in patients receiving dialysis and three in patients not receiving dialysis. The incidence of seroconversion was not increased with double-dose vaccination overall [risk ratio (RR) 1.17, 95% confidence interval (CI) 0.98-1.39], by dialysis requirement or vaccine type. The incidence of seroprotection (reported by only four studies) was increased with double-dose vaccination overall (RR 1.53, 95% CI 1.17-2.00) but not by dialysis requirement. Adverse events were not reported by treatment arm, precluding comparison. The overall quality of included studies was moderate to low. Conclusions The current data do not support clinical guideline recommendations for administering double-dose vaccination for patients with CKD as seroconversion was not improved and seroprotection was inadequately assessed. Large high-quality studies are required to overcome the current evidence gap regarding vaccine dosing in CKD.
Collapse
Affiliation(s)
- William R Mulley
- Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia.,Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, VIC, Australia
| | - Suong T T Le
- Department of Gastroenterology and Hepatology, Monash Medical Centre, Clayton, VIC, Australia.,School of Clinical Sciences, Monash University, Clayton, VIC, Australia
| | - Kathryn E Ives
- Department of Anaesthesia, Pain and Perioperative Medicine, Barwon Health-University Hospital Geelong, Geelong, VIC, Australia
| |
Collapse
|
|
20
|
Cimica V, Galarza JM. Adjuvant formulations for virus-like particle (VLP) based vaccines. Clin Immunol 2017; 183:99-108. [PMID: 28780375 DOI: 10.1016/j.clim.2017.08.004] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Revised: 06/11/2017] [Accepted: 08/01/2017] [Indexed: 12/13/2022]
Abstract
The development of virus-like particle (VLP) technology has had an enormous impact on modern vaccinology. In order to optimize the efficacy and safety of VLP-based vaccines, adjuvants are included in most vaccine formulations. To date, most licensed VLP-based vaccines utilize the classic aluminum adjuvant compositions. Certain challenging pathogens and weak immune responder subjects may require further optimization of the adjuvant formulation to maximize the magnitude and duration of the protective immunity. Indeed, novel classes of adjuvants such as liposomes, agonists of pathogen recognition receptors, polymeric particles, emulsions, cytokines and bacterial toxins, can be used to further improve the immunostimulatory activity of a VLP-based vaccine. This review describes the current advances in adjuvant technology for VLP-based vaccines directed at viral diseases, and discusses the basic principles for designing adjuvant formulations for enhancing the vaccine immunogenicity.
Collapse
Affiliation(s)
- Velasco Cimica
- TechnoVax, Inc., 765 Old Saw Mill River Road, Tarrytown, NY 10591, United States
| | - Jose M Galarza
- TechnoVax, Inc., 765 Old Saw Mill River Road, Tarrytown, NY 10591, United States.
| |
Collapse
|
|
21
|
Ogawa Y, Takei H, Ogawa R, Mihara K. Safety of human papillomavirus vaccines in healthy young women: a meta-analysis of 24 controlled studies. J Pharm Health Care Sci 2017; 3:18. [PMID: 28702209 PMCID: PMC5504559 DOI: 10.1186/s40780-017-0087-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 06/27/2017] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Human papillomavirus (HPV) vaccines have been shown to be effective for the eradication of HPV and prevention of cervical cancer. However, the number of women who receive HPV vaccinations has decreased over the last several years in Japan, due to concerns about adverse reactions associated with the vaccines. We evaluated the safety of three types of HPV vaccines separately in young women and the difference in the risk of adverse reactions between HPV and other vaccines by conducting a meta-analysis. METHODS Primary literature was retrieved from MEDLINE, the Cochrane Central Register of Controlled Trials, and Japana Centra Revuo Medicina. Prospective controlled studies with participants consisting exclusively of healthy women who received bivalent, quadrivalent, or 9-valent HPV (2vHPV, 4vHPV or 9vHPV) vaccines were included. Primary safety outcome was the incidence of solicited local and systemic symptoms, and unsolicited symptoms. When two or more studies were found for the same analysis, a meta-analysis was applied. RESULTS A total of 24 controlled studies from 22 articles were included in our study. Of the 24 studies, 16 were placebo-controlled and eight were active-controlled (different HPV vaccine or hepatitis vaccine). Average ages of the participants ranged from 12 to 37 years. A significantly higher incidence of solicited local symptoms was observed following injection of HPV vaccines (2vHPV and 4vHPV) compared to placebo, but there was no difference between HPV vaccines [risk ratio (RR) for 2vHPV: 1.25, 95% confidence interval (CI): 1.09 to 1.43, RR for 4vHPV: 1.16, 95% CI: 1.11 to 1.20]. The incidence of solicited systemic symptoms was not different between HPV vaccines and placebo (RR: 1.04, 95% CI: 0.99 to 1.09). The incidence of unsolicited symptoms was significantly higher for 2vHPV vaccine compared to placebo (RR: 1.28, 95% CI: 1.01 to 1.63), but was not significantly different between 2vHPV and hepatitis B vaccines. CONCLUSIONS HPV vaccines had significantly higher risk of any injection site symptom compared to placebo or other vaccines (hepatitis A and B vaccines), and the incidence of solicited local symptoms was no difference between 2vHPV vaccination and 4vHPV vaccination. However, the most adverse reactions were transient.
Collapse
Affiliation(s)
- Yukari Ogawa
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi Nishitokyo-shi, Tokyo, 202-8585 Japan
| | - Hinako Takei
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi Nishitokyo-shi, Tokyo, 202-8585 Japan
| | - Ryuichi Ogawa
- Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588 Japan
| | - Kiyoshi Mihara
- Faculty of Pharmacy, Department of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi Nishitokyo-shi, Tokyo, 202-8585 Japan
| |
Collapse
|
|
22
|
Kim JU, Kim M, Kim S, Nguyen TT, Kim E, Lee S, Kim S, Kim H. Dendritic Cell Dysfunction in Patients with End-stage Renal Disease. Immune Netw 2017; 17:152-162. [PMID: 28680376 PMCID: PMC5484645 DOI: 10.4110/in.2017.17.3.152] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Revised: 04/06/2017] [Accepted: 04/10/2017] [Indexed: 02/07/2023] Open
Abstract
End-stage renal disease (ESRD) with immune disorder involves complex interactions between the innate and adaptive immune responses. ESRD is associated with various alterations in immune function such as a reduction in polymorphonuclear leukocyte bactericidal activity, a suppression of lymphocyte proliferative response to stimuli, and a malfunction of cell-mediated immunity at the molecular level. ESRD also increases patients' propensity for infections and malignancies as well as causing a diminished response to vaccination. Several factors influence the immunodeficiency in patients with ESRD, including uremic toxins, malnutrition, chronic inflammation, and the therapeutic dialysis modality. The alteration of T-cell function in ESRD has been considered to be a major factor underlying the impaired adaptive cellular immunity in these patients. However, cumulative evidence has suggested that the immune defect in ESRD can be caused by an Ag-presenting dendritic cell (DC) dysfunction in addition to a T-cell defect. It has been reported that ESRD has a deleterious effect on DCs both in terms of their number and function, although the precise mechanism by which DC function becomes altered in these patients is unclear. In this review, we discuss the effects of ESRD on the number and function of DCs and propose a possible molecular mechanism for DC dysfunction. We also address therapeutic approaches to improve immune function by optimally activating DCs in patients with ESRD.
Collapse
Affiliation(s)
- Ji Ung Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
| | - Miyeon Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
| | - Sinae Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Tam Thanh Nguyen
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Eunhye Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea
| | - Siyoung Lee
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,YbdYbiotech research center, Seoul 08589, Korea
| | - Soohyun Kim
- Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea.,College of Veterinary Medicine, Veterinary Science Research Institute, Konkuk University, Seoul 05029, Korea
| | - Hyunwoo Kim
- Division of Nephrology, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju 63241, Korea
| |
Collapse
|
|
23
|
Abstract
Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.
Collapse
|
|
24
|
Abstract
Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s. Vaccination against hepatitis B virus infection has proved highly successful in reducing the disease burden, the development of the carrier state and the hepatitis B-related morbidity and mortality in the countries where vaccination has been implemented. Despite success and efficacy of preventive vaccines, a huge number of chronically infected patients still remain. Therapeutic vaccination may prove to be useful coupled with current antivirals and other immunomodulatory approaches to treat these patients. This review summarizes current unresolved issues and future perspectives on vaccination required for global cure of hepatitis B virus infection.
Collapse
Affiliation(s)
- Marie-Louise Michel
- Laboratoire PVHB, Bâtiment Lwoff, Inserm U994, Institut Pasteur, 28, rue du Docteur Roux, 75015 Paris, France
| |
Collapse
|
|
25
|
Varikuti S, Oghumu S, Natarajan G, Kimble J, Sperling RH, Moretti E, Kaplan MH, Satoskar AR. STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity. Int Immunol 2016; 28:565-570. [PMID: 27578456 DOI: 10.1093/intimm/dxw038] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 08/19/2016] [Indexed: 01/14/2023] Open
Abstract
STAT4 is critical for the production of IFN-γ during the generation of Th1 immune responses. We investigated the role of STAT4 in mediating Th1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN-γ production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and Th2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KO-derived splenocytes. Our observations for defective Th1 and Th2 responses in STAT4KO mice were further supported by the low levels of Th1-associated IgG2a and Th2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both Th1 and Th2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development.
Collapse
Affiliation(s)
- Sanjay Varikuti
- Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA
| | - Steve Oghumu
- Department of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA
| | - Gayathri Natarajan
- Department of Microbiology, Ohio State University, Columbus, OH 43210, USA
| | - Jennifer Kimble
- Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA
| | - Rachel H Sperling
- Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA
| | - Ellen Moretti
- Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA
| | - Mark H Kaplan
- Department of Pediatrics, Indiana University, Indianapolis, IN 46202, USA
| | - Abhay R Satoskar
- Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA .,Department of Microbiology, Ohio State University, Columbus, OH 43210, USA
| |
Collapse
|
|
26
|
Buonsanti C, Balocchi C, Harfouche C, Corrente F, Galli Stampino L, Mancini F, Tontini M, Malyala P, Bufali S, Baudner B, De Gregorio E, Valiante NM, O'Hagan DT, Rappuoli R, D'Oro U. Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines. Sci Rep 2016; 6:29063. [PMID: 27439378 PMCID: PMC4954951 DOI: 10.1038/srep29063] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2016] [Accepted: 06/13/2016] [Indexed: 01/05/2023] Open
Abstract
Although glycoconjugate vaccines are generally very efficacious, there is still a need to improve their efficacy, especially in eliciting a strong primary antibody response. We have recently described a new type of vaccine adjuvant based on a TLR7 agonist adsorbed to alum (Alum-TLR7), which is highly efficacious at enhancing immunogenicity of protein based vaccines. Since no adjuvant has been shown to potentiate the immune response to glycoconjugate vaccines in humans, we investigated if Alum-TLR7 is able to improve immunogenicity of this class of vaccines. We found that in a mouse model Alum-TLR7 greatly improved potency of a CRM197-MenC vaccine increasing anti-MenC antibody titers and serum bactericidal activity (SBA) against MenC compared to alum adjuvanted vaccine, especially with a low dose of antigen and already after a single immunization. Alum-TLR7 also drives antibody response towards Th1 isotypes. This adjuvant was also able to increase immunogenicity of all polysaccharides of a multicomponent glycoconjugate vaccine CRM197-MenACWY. Furthermore, we found that Alum-TLR7 increases anti-polysaccharide immune response even in the presence of a prior immune response against the carrier protein. Finally, we demonstrate that Alum-TLR7 adjuvant effect requires a functional TLR7. Taken together, our data support the use of Alum-TLR7 as adjuvant for glycoconjugate vaccines.
Collapse
|
|
27
|
Vilajeliu A, Sequera VG, García-Basteiro AL, Sicuri E, Aldea M, Velasco C, Bayas JM. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients. Hum Vaccin Immunother 2016; 12:2317-21. [PMID: 27105182 DOI: 10.1080/21645515.2016.1168955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.
Collapse
Affiliation(s)
- Alba Vilajeliu
- a Department of Preventive Medicine and Epidemiology , Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain
| | - Víctor-Guillermo Sequera
- a Department of Preventive Medicine and Epidemiology , Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain
| | - Alberto L García-Basteiro
- b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,c Centro de Investigação em Saúde de Manhiça (CISM) , Maputo , Mozambique.,d Amsterdam Institute for Global Health and Development (AIGHD) , Amsterdam , The Netherlands
| | - Elisa Sicuri
- b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,e Department of Infectious Disease Epidemiology , Health Economics Group, School of Public Health, Imperial College London , London , UK
| | - Marta Aldea
- a Department of Preventive Medicine and Epidemiology , Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain
| | - César Velasco
- a Department of Preventive Medicine and Epidemiology , Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain
| | - José M Bayas
- a Department of Preventive Medicine and Epidemiology , Hospital Clínic - Universitat de Barcelona , Barcelona , Spain.,b ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona , Barcelona , Spain
| |
Collapse
|
|
28
|
Novel Perspectives on the Hepatitis B Virus Vaccine in the Chronic Kidney Disease Population. Int J Artif Organs 2016; 38:625-31. [DOI: 10.5301/ijao.5000458] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/30/2015] [Indexed: 01/05/2023]
Abstract
Background The prevalence and incidence rates of hepatitis B virus (HBV) among patients undergoing maintenance dialysis in developed countries have declined over the last 2 decades thanks to the implementation of numerous infection control procedures in dialysis units, including the hepatitis B vaccine. It is well known that the immune response against HBV vaccine is unsatisfactory in the chronic kidney disease (CKD) population. The seroprotection rate after the HB vaccine schedule is low and the anti-HB titers are reduced, falling logarithmically over time. Purpose We did an extensive review of the medical literature on the mechanisms underlying the reduced response rate towards the HBV vaccine in patients with CKD. The efficacy and safety of HBV vaccines for use in the CKD population was also evaluated. Results Currently available vaccines against HBV are mostly plasma-derived or manufactured by recombinant DNA technology (yielding the S protein of the HBV envelope). The most promising strategy to enhance the immune response toward the HBV vaccine in the dialysis population is given by adjuvanted vaccines. Second-generation recombinant HB vaccines provided with a novel adjuvant (AS04, made of 3- O-4′-desacyl-monophosphoryl lipid A adsorbed on aluminum phosphate) demonstrated improved immunogenicity but a number of patients with an unsatisfactory response still occurs. Additional second-generation vaccines containing nonaluminum-based adjuvant systems such as AS02 (3- O-desacyl-4′-monophoshoryl lipid A and QS21) or 1018 (a Toll-like receptor 9 agonist) have shown higher immunogenicity and acceptable safety in the CKD population. The evidence in patients with end-stage renal disease is extremely limited on the use of third-generation vaccines, recombinant HBV vaccines expressed in mammalian cells containing S/Pre-S antigens. Conclusions The immunogenicity of HBV vaccines in patients with CKD is suboptimal but novel technologies promise to give better results in the near future.
Collapse
|
|
29
|
Apostólico JDS, Boscardin SB, Yamamoto MM, de Oliveira-Filho JN, Kalil J, Cunha-Neto E, Rosa DS. HIV Envelope Trimer Specific Immune Response Is Influenced by Different Adjuvant Formulations and Heterologous Prime-Boost. PLoS One 2016; 11:e0145637. [PMID: 26727218 PMCID: PMC4699765 DOI: 10.1371/journal.pone.0145637] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Accepted: 12/07/2015] [Indexed: 02/07/2023] Open
Abstract
The development of a preventive vaccine against human immunodeficiency virus (HIV-1) infection is the most efficient method to control the epidemic. The ultimate goal is to develop a vaccine able to induce specific neutralizing, non-neutralizing antibodies and cellular mediated immunity (CMI). Humoral and CMI responses can be directed to glycoproteins that are normally presented as a trimeric spike on the virus surface (gp140). Despite safer, subunit vaccines are normally less immunogenic/effective and need to be delivered together with an adjuvant. The choice of a suitable adjuvant can induce effective humoral and CMI that utterly lead to full protection against disease. In this report, we established a hierarchy of adjuvant potency on humoral and CMI when admixed with the recombinant HIV gp140 trimer. We show that vaccination with gp140 in the presence of different adjuvants can induce high-affinity antibodies, follicular helper T cells and germinal center B cells. The data show that poly (I:C) is the most potent adjuvant to induce specific CMI responses evidenced by IFN-γ production and CD4+/CD8+ T cell proliferation. Furthermore, we demonstrate that combining some adjuvants like MPL plus Alum and MPL plus MDP exert additive effects that impact on the magnitude and quality of humoral responses while mixing MDP with poly (I:C) or with R848 had no impact on total IgG titers but highly impact IgG subclass. In addition, heterologous DNA prime- protein boost yielded higher IgG titers when compare to DNA alone and improved the quality of humoral response when compare to protein immunization as evidenced by IgG1/IgG2a ratio. The results presented in this paper highlight the importance of selecting the correct adjuvant-antigen combination to potentiate desired cells for optimal stimulation.
Collapse
Affiliation(s)
- Juliana de Souza Apostólico
- Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
| | - Silvia Beatriz Boscardin
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Márcio Massao Yamamoto
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Jethe Nunes de Oliveira-Filho
- Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
| | - Jorge Kalil
- Heart Institute (InCor), University of São Paulo—School of Medicine, São Paulo, Brazil
- Institute for Investigation in Immunology—INCT, São Paulo, Brazil
| | - Edecio Cunha-Neto
- Heart Institute (InCor), University of São Paulo—School of Medicine, São Paulo, Brazil
- Institute for Investigation in Immunology—INCT, São Paulo, Brazil
- Laboratory of Clinical Immunology and Allergy—LIM60, University of São Paulo- School of Medicine, São Paulo, Brazil
| | - Daniela Santoro Rosa
- Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
- Institute for Investigation in Immunology—INCT, São Paulo, Brazil
- * E-mail:
| |
Collapse
|
|
30
|
Fabrizi F, Tarantino A, Castelnovo C, Martin P, Messa P. Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study. Kidney Blood Press Res 2015; 40:584-92. [PMID: 26566033 DOI: 10.1159/000368534] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2015] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/AIMS Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04) has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. METHODS Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. RESULTS 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84%) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57) with lower GMCs (62.74 mIU/mL, P<0.0001). Multivariate analysis revealed a detrimental role of age on the immune response to HB-AS04 vaccine (F Ratio, 4.04; P<0.04). Tolerance to HBV-AS04 was good and only minor side-effects were observed. CONCLUSIONS HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.
Collapse
Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital and IRCCS Foundation, Milano, Italy
| | | | | | | | | |
Collapse
|
|
31
|
Seiz PL, Slanina H, Ziebuhr J, Gerlich WH, Glebe D, Schüttler CG. Studies of nosocomial outbreaks of hepatitis B in nursing homes in Germany suggest a major role of hepatitis B e antigen expression in disease severity and progression. Int J Med Microbiol 2015; 305:663-72. [PMID: 26338147 DOI: 10.1016/j.ijmm.2015.08.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) causes acute or chronic hepatitis B. Local outbreaks of HBV infections in skilled nursing facilities is a matter of growing concern in developed countries. Here, we investigated two outbreaks of hepatitis B that recently occurred in nursing homes in Germany. The outbreak at location A was associated with acute fulminant hepatitis with fatal outcome in several cases, while individuals infected at location B developed asymptomatic or mild hepatitis B. Sequence analysis of viruses involved in these outbreaks revealed different, but unique HBV strains for each location. Each of the strains produced high viremia of more than 10(9) virions/mL serum. We found that the mild course of hepatitis B at location B was caused by a circulating wild-type HBV genotype A2 strain, which is commonly found in Central Europe. Complete genome sequences of isolates obtained from infected patients revealed nearly 100% sequence identity at the nucleotide level as well as expression of HBV e protein (HBeAg), a known T cell tolerogen in the incubation or chronic phases of HBV infection. By contrast, the outbreak at location A was associated with an HBV genotype D2 variant that lacked HBeAg expression, suggesting that immunopathology and selection of specific HBV variants played a major role in the severe (or even fulminant) acute hepatitis observed at location A. Importantly, all patients were diagnosed with type 2 diabetes mellitus, a known risk factor for healthcare-associated transmission of HBV. The study leads us to suggest that, besides strict adherence to hygiene standards, additional efforts are required to reduce the risk of HBV transmission and fulminant disease progression in healthcare settings and nursing homes. In this context, a general screening for HBsAg and active hepatitis B vaccination should be considered for people living in nursing homes, especially for those with diagnosed diabetes or other predisposing factors for HBV transmission.
Collapse
Affiliation(s)
- Pia L Seiz
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany
| | - Heiko Slanina
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany
| | - John Ziebuhr
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany
| | - Wolfram H Gerlich
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany
| | - Dieter Glebe
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany.
| | - Christian G Schüttler
- Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research, Biomedical Research Center Seltersberg, Schubertstr. 81, 35392 Giessen, Germany
| |
Collapse
|
|
32
|
Tajiri K, Shimizu Y. Unsolved problems and future perspectives of hepatitis B virus vaccination. World J Gastroenterol 2015; 21:7074-7083. [PMID: 26109794 PMCID: PMC4476869 DOI: 10.3748/wjg.v21.i23.7074] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 03/23/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is still a serious worldwide problem, and vaccination is the most effective strategy for primary prevention of the infection. Although universal vaccination may be required for total eradication, several countries, including Japan, have not yet adopted universal vaccination programs. Some individuals are non-responders to HBV vaccine and several mechanisms responsible for their poor response have been proposed. To overcome non-response, third generation vaccines with pre-S proteins have been developed. These vaccines have shown better anti-HBs responses and may also be effective in preventing infection by HBV with S mutant. Improvement of vaccine efficacy by intradermal administration, or co-administration with cytokines or adjuvants, may also be effective in non-responders. The necessity, timing and method of booster vaccination in responders with decreased anti-HBs responses, and effective vaccination against S-mutant HBV, are issues requiring resolution in the global prevention of HBV infection.
Collapse
|
|
33
|
Abstract
Hepatitis outbreaks in hemodialysis (HD) patients and staff were reported in the late 1960s, and a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in HD centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin and segregation of HBV carriers. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus (HCV) is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge; however, pegylation of interferon-alfa has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus, hepatitis GB virus C and the TT virus. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of HD. Major recent advances in the viral diagnosis technology and the development of new oral, direct-acting antiviral agents allow early diagnosis and better therapeutic response. The current update will review the recent developments, controversies and new treatment of viral hepatitis in HD patients.
Collapse
Affiliation(s)
- Bassam Bernieh
- Consultant and Chief of Nephrology, Tawam Hospital in Affiliation with Johns Hopkins Medicine, Clinical Professor of Medicine, COMHS, UAE University, Al Ain, UAE
| |
Collapse
|
|
34
|
Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Factors affecting effectiveness of vaccination against hepatitis B virus in hemodialysis patients. World J Gastroenterol 2014; 20:12018-12025. [PMID: 25232238 PMCID: PMC4161789 DOI: 10.3748/wjg.v20.i34.12018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/29/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is a major global health problem. Despite the success of the general measures against blood transmitted infections in hemodialysis (HD) units, the prevalence of HBV infection among the HD patients is still high. Thus vaccination against HBV is indicating in this population. However, compared with the general population the seroprotection achieved in HD patients remains relatively low, at about 70%. In this review patient, HD procedure and vaccine-associated factors that affect the efficacy of HBV vaccination are analyzed. Also alternative routes of HBV vaccine administration as well as new and more immunogenic vaccine formulations are discussed. However, besides scientific progress, vigilance of HD physicians and staff regarding the general measures against the transmission of blood borne infections and the vaccination against HBV is also required for reducing the prevalence of this viral infection.
Collapse
|
|
35
|
Grzegorzewska AE. Hepatitis B vaccination in chronic kidney disease patients: a call for novel vaccines. Expert Rev Vaccines 2014; 13:1317-26. [PMID: 25148051 DOI: 10.1586/14760584.2014.944508] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The protective immunization rates in response to hepatitis B vaccination in chronic kidney disease (CKD) patients are lower than response rates in the general population because of genetic and CKD-related factors as well as logistic problems with a proper providing of the recommended vaccination schedules. This review focuses on third-generation vaccines and adjuvanted vaccines commercially introduced in some countries, investigated in clinical trials, especially involving CKD patients or used only in the experimental studies. In order to improve the immunization rate, the use of third-generation vaccines (yeast-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S2/S HBV vaccines, mammalian cell-derived pre-S1/pre-S2/S HBV vaccines), novel adjuvants (AS04, AS02, phosphorothioate oligodeoxyribonucleotide, hemokinin-1, a polysaccharide based on delta inulin, nano-complex Hep-c, cyclic diguanylate) or immunostimulants for enhancement of immunogenicity of existing recombinant hepatitis B vaccines is tried to improve results of hepatitis B vaccination prior to dialysis commencement or already on renal replacement therapy.
Collapse
Affiliation(s)
- Alicja E Grzegorzewska
- Chair and Department of Nephrology, Transplantology and Internal Diseases Poznań University of Medical Sciences (PUMS), 60-355 Poznań, 49 Przybyszewskiego Blvd Poznań, Poland
| |
Collapse
|
|
36
|
Levast B, Awate S, Babiuk L, Mutwiri G, Gerdts V, van Drunen Littel-van den Hurk S. Vaccine Potentiation by Combination Adjuvants. Vaccines (Basel) 2014; 2:297-322. [PMID: 26344621 PMCID: PMC4494260 DOI: 10.3390/vaccines2020297] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Revised: 03/22/2014] [Accepted: 03/28/2014] [Indexed: 01/02/2023] Open
Abstract
Adjuvants are crucial components of vaccines. They significantly improve vaccine efficacy by modulating, enhancing, or extending the immune response and at the same time reducing the amount of antigen needed. In contrast to previously licensed adjuvants, current successful adjuvant formulations often consist of several molecules, that when combined, act synergistically by activating a variety of immune mechanisms. These "combination adjuvants" are already registered with several vaccines, both in humans and animals, and novel combination adjuvants are in the pipeline. With improved knowledge of the type of immune responses needed to successfully induce disease protection by vaccination, combination adjuvants are particularly suited to not only enhance, but also direct the immune responses desired to be either Th1-, Th2- or Th17-biased. Indeed, in view of the variety of disease and population targets for vaccine development, a panel of adjuvants will be needed to address different disease targets and populations. Here, we will review well-known and new combination adjuvants already licensed or currently in development-including ISCOMs, liposomes, Adjuvant Systems Montanides, and triple adjuvant combinations-and summarize their performance in preclinical and clinical trials. Several of these combination adjuvants are promising having promoted improved and balanced immune responses.
Collapse
Affiliation(s)
- Benoît Levast
- VIDO-Intervac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
| | - Sunita Awate
- VIDO-Intervac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
| | - Lorne Babiuk
- University Hall, University of Alberta, Edmonton, AB T6G 2J9, Canada.
| | - George Mutwiri
- VIDO-Intervac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
- School of Public Health, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
| | - Volker Gerdts
- VIDO-Intervac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
- Veterinary Microbiology, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada.
| | - Sylvia van Drunen Littel-van den Hurk
- VIDO-Intervac, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK S7N 5E3, Canada.
- Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
| |
Collapse
|
|
37
|
Soni R, Horowitz B, Unruh M. Immunization in end-stage renal disease: opportunity to improve outcomes. Semin Dial 2013; 26:416-26. [PMID: 23751048 DOI: 10.1111/sdi.12101] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Infection is the second most common cause of death in patients with end-stage renal disease (ESRD), following cardiovascular causes. Immunization is a fairly simple, but underutilized, strategy for prevention of infectious morbidity and mortality in patients with kidney failure. It is imperative for nephrologists and primary care providers to have an understanding of immunization as an essential component of preventive healthcare measures in this high-risk population. Patients with ESRD represent a unique population due to their immunosuppressed state, dialysis-related exposures and suboptimal response to routine vaccines. While the Advisory Committee on Immunization Practices (ACIP) provides guidelines for vaccination of patients with renal disease against Hepatitis B, influenza and pneumococcal disease, the data on immunization against other commonly preventable infectious diseases are lacking. This article reviews the recent evidence on immunization in the ESRD population and synthesizes the related implications for maximizing prevention of infectious diseases in this high-risk population.
Collapse
Affiliation(s)
- Ritu Soni
- Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | | |
Collapse
|
|
38
|
Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. THE LANCET. INFECTIOUS DISEASES 2013; 12:966-76. [PMID: 23174382 DOI: 10.1016/s1473-3099(12)70243-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV.
Collapse
|
|
39
|
Hepatitis B vaccines. Vaccines (Basel) 2013. [DOI: 10.1016/b978-1-4557-0090-5.00025-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
|
|
40
|
Sanadgol H. Levamisole usage as an adjuvant to hepatitis B vaccine in hemodialysis patients, yes or no? Nephrourol Mon 2012; 5:673-8. [PMID: 23577329 PMCID: PMC3614321 DOI: 10.5812/numonthly.3985] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2011] [Revised: 01/30/2012] [Accepted: 02/24/2012] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is much more common in hemodialysis patients than the general population. These patients have an impaired immune response to HBV vaccination; to that end there are certain studies that have evaluated levamisole as an immunomodulator agent improving HBV vaccination response rate in hemodialysis patients. OBJECTIVES In the current review, we have assembled all of the results to determine whether lavamisole is of value as an adjuvant to HBV vaccination in hemodialysis patients. MATERIALS AND METHODS Science Direct (Elsevier), ProQuest, Springer, MD Consult, BMJ Journals, Pubmed and Wiley were searched for levamisole application to HBV vaccination in hemodialysis patients. All studies revealed a seroconversion response level between levamisole plus HBV vaccine versus HBV vaccine alone. RESULTS From 10 relevant studies, 5 studies fulfilled our inclusion criteria. Three of them suggested the significant benefit of adding levamisole to the HBV vaccine to increase augment seroprotection level in hemodialysis patients. Another study reported a decrease in seroprotection level and another study showed no significant difference caused by levamisole administration. CONCLUSIONS Due to the limited number of studies evaluated, it is challenging to perform a definite decision about routinely administering levamisole in addition to the HBV vaccine for all hemodialysis patients. However, it does seem reasonable to recommend administration of levamisole for impaired immune response patients.
Collapse
Affiliation(s)
- Houshang Sanadgol
- Department of Nephrology, Faculty of Medicine, Zahedan Medical University, Zahedan, IR Iran
| |
Collapse
|
|
41
|
Somi MH, Hajipour B. Improving hepatitis B vaccine efficacy in end-stage renal diseases patients and role of adjuvants. ISRN GASTROENTEROLOGY 2012; 2012:960413. [PMID: 23029621 PMCID: PMC3458294 DOI: 10.5402/2012/960413] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/18/2012] [Accepted: 08/01/2012] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) infection is a serious global health problem.The prevalence of viral hepatitis is higher in dialysis patients than in the general population because of the opportunity for exposure during the dialysis procedure. Immunization is the most effective way to prevent transmission of hepatitis B virus (HBV) and hence the development of acute or chronic hepatitis B. It is well established that patients with end-stage renal disease including dialysis-dependent patients, have an impaired immune response to hepatitis B vaccine. End stage renal diseases (ESRD) patients have lower seroconversion rates compared with the subjects with intact renal function. Moreover, even after the completion of vaccination schedule anti-hepatitis B (anti-HBs) titers of responder dialysis, patients are low and decline logarithmically with time. The impaired efficacy of HBV vaccine in patients with ESRD has been attributed to numerous factors such as immune compromise because of uremia and some other factors. One approach to improve the immunogenicity of existing HBV vaccines is adjuvantation, and it's very important to find more effective adjutants for improving HBV vaccine efficacy. In this paper we have a brief review on recently known new ways for improving HBV vaccine efficacy.
Collapse
Affiliation(s)
- Mohammad Hossein Somi
- Liver and Gastroenterology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | |
Collapse
|
|
42
|
Neu AM. Immunizations in children with chronic kidney disease. Pediatr Nephrol 2012; 27:1257-63. [PMID: 22048175 PMCID: PMC3382633 DOI: 10.1007/s00467-011-2042-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Revised: 10/04/2011] [Accepted: 10/05/2011] [Indexed: 11/29/2022]
Abstract
Children with chronic kidney disease (CKD) are at increased risk for vaccine-preventable diseases. These patients may have a reduced response to and/or reduced duration of antibody after immunization and therefore monitoring of antibody levels or titers is indicated for some vaccines. In addition, pediatric CKD patients require immunizations not routinely provided to healthy children. Unfortunately, studies in pediatric CKD patients, including those on dialysis and awaiting kidney transplantation, have demonstrated sub-optimal immunization rates. In order to minimize the risk for vaccine-preventable disease in pediatric CKD patients, it is imperative that all who care for these patients remain abreast of the recommended childhood immunization schedule, as well as alterations to this schedule required for children with CKD, including end-stage kidney disease. This article reviews recent changes to the recommended childhood immunization schedule and alterations and additions to this schedule recommended for children with CKD. Where available, data on antibody response to immunizations in children with CKD are presented.
Collapse
Affiliation(s)
- Alicia M Neu
- Pediatric Nephrology, The Johns Hopkins University School of Medicine, 200 North Wolfe Street, Room 3065, Baltimore, MD 21287, USA.
| |
Collapse
|
|
43
|
Seybold U, Schelling J, Münchhoff M, Bogner JR. [Vaccination strategies for adults]. MMW Fortschr Med 2012; 154:47-50. [PMID: 22838132 DOI: 10.1007/s15006-012-0746-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Affiliation(s)
- Ulrich Seybold
- Sektion Klinische Infektiologie, Medizinische Klinik und Poliklinik IV, Klinikum der Universität Miünchen.
| | | | | | | |
Collapse
|
|
44
|
Hepatitis B virus vaccine in chronic kidney disease: improved immunogenicity by adjuvants? A meta-analysis of randomized trials. Vaccine 2012; 30:2295-300. [PMID: 22285268 DOI: 10.1016/j.vaccine.2012.01.064] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2011] [Accepted: 01/19/2012] [Indexed: 01/10/2023]
Abstract
BACKGROUND Patients with chronic kidney disease typically show an impaired immune response to hepatitis B virus vaccine compared with healthy individuals. A variety of inherited or acquired factors have been implicated in this diminished response. Some authors suggested a benefit with adjuvantation to improve the immunogenicity of existing HBV vaccines. AIM To evaluate the efficacy and safety of adjuvantation for hepatitis B virus vaccine in patients with chronic kidney disease. METHODS Only prospective, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird with heterogeneity and subgroups analyses. The primary end-point of interest was the seroprotection rate after HBV vaccination with recombinant vaccine plus adjuvants (study group) versus recombinant vaccine alone (control group). RESULTS We identified ten studies involving 1228 unique patients with chronic kidney disease. Pooling of study results did not show a significant increase in seroprotection rate among study (HBV recombinant vaccine plus adjuvants) versus control (HBV recombinant alone) patients; the pooled odds ratio of seroprotection rate was 1.47 (95% CI: 0.88; 2.46, NS). The pooled OR for seroresponse rate after HBV vaccine (adjuvanted recombinant vaccine versus recombinant vaccine alone) did not change in the subgroup of studies based on novel adjuvant systems (i.e., HBV-AS04 or HBV-AS02), the pooled OR was 2.22 (95% CI, 0.72; 6.78), NS. Q-test for heterogeneity being 10.819 (P=0.004). CONCLUSIONS Our meta-analysis showed that adjuvanted hepatitis B vaccine did not significantly improve the seroprotection rate in patients with renal insufficiency. These results do not support adjuvantation as an approach to increase the immunogenicity of existing recombinant vaccines towards HBV in this high-risk population.
Collapse
|
|
45
|
Garçon N, Van Mechelen M. Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Expert Rev Vaccines 2011; 10:471-86. [PMID: 21506645 DOI: 10.1586/erv.11.29] [Citation(s) in RCA: 242] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The immunostimulants 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and the saponin QS-21 are part of licensed or candidate vaccines. MPL and QS-21 directly affect the innate immune response to orchestrate the quality and intensity of the adaptive immune response to the vaccine antigens. The combination of immunostimulants in different adjuvant formulations forms the basis of Adjuvant Systems (AS) as a way to promote appropriate protective immune responses following vaccination. MPL and aluminum salts are present in AS04, and both MPL and QS-21 are present in AS01 and AS02, which are liposome- and emulsion-based formulations, respectively. The recent clinical performance of AS01-, AS02- and AS04-adjuvanted vaccines will be discussed in the context of the diseases being targeted. The licensing of two AS04-adjuvanted vaccines and the initiation of Phase III trials with an AS01-adjuvanted vaccine demonstrate the potential to develop new or improved human vaccines that contain MPL or MPL and QS-21.
Collapse
|
|
46
|
Geddes C, Lindley E, Duncan N. Renal Association Clinical Practice Guideline on prevention of blood borne virus infection in the renal unit. Nephron Clin Pract 2011; 118 Suppl 1:c165-88. [PMID: 21555895 DOI: 10.1159/000328068] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2009] [Accepted: 07/14/2009] [Indexed: 01/17/2023] Open
|
|
47
|
Kalia H, Fabrizi F, Martin P. Hepatitis B virus and renal transplantation. Transplant Rev (Orlando) 2011; 25:102-9. [PMID: 21530218 DOI: 10.1016/j.trre.2011.02.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Hepatitis B virus (HBV) infection remains an important cause of liver disease in the renal transplant (RT) population, potentially diminishing survival. Consequences of HBV infection after RT include progression to decompensated cirrhosis and an increased risk of hepatocellular carcinoma. Although precautions initially recommended by the Centers for Diseases Control and Prevention 30 years ago have substantially reduced HBV transmission within hemodialysis units, acute HBV outbreaks continue to be reported in patients with chronic kidney disease on maintenance hemodialysis. In addition, immigration from areas of high HBV prevalence implies that HBV-infected organs with chronic kidney disease will continue to enter the RT pool. Fortunately, the advent of oral therapy for HBV infection now reduces the risk of HBV progression post-RT.
Collapse
Affiliation(s)
- Harmit Kalia
- Division of Hepatology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
| | | | | |
Collapse
|
|
48
|
Steinhagen F, Kinjo T, Bode C, Klinman DM. TLR-based immune adjuvants. Vaccine 2011; 29:3341-55. [PMID: 20713100 PMCID: PMC3000864 DOI: 10.1016/j.vaccine.2010.08.002] [Citation(s) in RCA: 378] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2010] [Revised: 07/27/2010] [Accepted: 08/01/2010] [Indexed: 12/29/2022]
Abstract
This work describes the nature and strength of the immune response induced by various Toll-like receptor ligands and their ability to act as vaccine adjuvants. It reviews the various ligands capable of triggering individual TLRs, and then focuses on the efficacy and safety of those agents for which clinical results are available.
Collapse
Affiliation(s)
- Folkert Steinhagen
- Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, United States
| | | | | | | |
Collapse
|
|
49
|
A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice. Int Immunopharmacol 2011; 11:1195-204. [PMID: 21492746 DOI: 10.1016/j.intimp.2011.03.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Revised: 03/11/2011] [Accepted: 03/28/2011] [Indexed: 11/23/2022]
Abstract
Anthrax is an infectious disease caused by Bacillus anthracis. The currently licensed human anthrax vaccines contain protective antigen (PA) as a major protective component and alum as an adjuvant. In this study, we investigated whether CIA05, a TLR4 agonist, is able to promote the immune response to an anthrax vaccine adjuvanted with alum. BALB/c mice were immunized intraperitoneally three times at 2-week intervals with a recombinant B. anthracis PA alone or in combination with CIA05 in the absence or presence of alum, and immune responses were determined 2 or 3 weeks after the third immunization. The results showed that the combination of CIA05 and alum significantly increased both serum anti-PA IgG antibody and toxin-neutralizing antibody titers, and the adjuvant effects were greater when lower antigen doses were used for immunization. Both CIA05 and alum stimulated PA-specific splenocyte secretion of interleukin (IL)-4, IL-5, and IL-6. A combination of the two yielded synergistic effects on IL-4 secretion, but CIA05 tended to repress IL-5 and IL-6 secretions induced by alum. Co-administration of CIA05 and alum also increased GL7 expression in B220(+)CD24(+) splenic cells, indicating the ability to activate B cells. These data suggest that CIA05, combined with alum, could be used to achieve higher immune responses to PA, leading to the development of an effective anthrax vaccine.
Collapse
|
|
50
|
Hepatitis C virus soluble E2 in combination with QuilA and CpG ODN induces neutralizing antibodies in mice. Vaccine 2011; 29:2910-7. [PMID: 21338680 DOI: 10.1016/j.vaccine.2011.02.009] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 12/16/2010] [Accepted: 02/05/2011] [Indexed: 11/22/2022]
Abstract
Several studies have emphasized the importance of an early, highly neutralizing antibody response in the clearance of Hepatitis C virus (HCV) infection. The envelope glycoprotein E2 is a major target for HCV neutralizing antibodies. Here, we compared antibody responses in mice immunized with native soluble E2 (sE2) from the H77 1a isolate coupled with different adjuvants or combinations of adjuvants. Adjuvanting sE2 with Freund's, monophosphoryl lipid A (MPL), cytosine phosphorothioate guanine oligodeoxynucleotide (CpG ODN), or alpha-galactosylceramide (αGalCer) derivatives elicited only moderate antibody responses. In contrast, immunizations with sE2 and QuilA elicited exceptionally high anti-E2 antibody titers. Sera from these mice effectively neutralized HCV pseudoparticles (HCVpp) 1a entry. Moreover, the combination of QuilA and CpG ODN further enhanced neutralizing antibody titers wherein cross-neutralization of HCVpp 4 was observed. We conclude that the combination of QuilA and CpG ODN is a promising adjuvant combination that should be further explored for the development of an HCV subunit vaccine. Our work also emphasizes that the ideal combination of adjuvant and immunogen has to be determined empirically.
Collapse
|