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Marjani A, Alavian SM, Nassiri Toosi M, Alavian SH, Abazari MF, Khamseh A, Jazayeri SM. Hepatitis B virus infection after immunization: How serious it is? An updated review. Clin Exp Med 2025; 25:113. [PMID: 40210771 PMCID: PMC11985588 DOI: 10.1007/s10238-025-01645-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Accepted: 03/19/2025] [Indexed: 04/12/2025]
Abstract
Infection with hepatitis B virus (HBV) is one of the significant challenges worldwide. Despite the availability of antiviral drugs against this virus, the most critical strategy to prevent HBV infection is HB vaccination. Basically, despite widespread conventional HB vaccination, due to various reasons, including waning of hepatitis B surface antibody (HBsAb) titer after vaccination, the emergence of vaccine-escape mutants, failure to respond to the vaccine due to viral and host factors, levels of response in high-risk individuals and non-responders to conventional HB vaccination remains a major, unsolved and severe concern. This review focuses on the underlying reasons for conventional hepatitis B vaccination failures. It also suggests solutions to overcome these failures by highlighting significant advances in vaccination, including hepatitis B third-generation vaccines and adjuvanted hepatitis B vaccines as efficient alternatives to second-generation vaccines. Potentially, these new strategies will compensate for the shortcomings caused by second-generation vaccines. Adherence to these denouements has a significant role in preventing the circulation of HBV among individuals and reducing the global burden of HBV-related diseases.
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Affiliation(s)
- Arezoo Marjani
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohssen Nassiri Toosi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Division of Medical Sciences, Island Medical Program, University of British Columbia, Victoria, BC, Canada
| | - Azam Khamseh
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.
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Asri N, Mohammadi S, Jahdkaran M, Rostami-Nejad M, Rezaei-Tavirani M, Mohebbi SR. Viral infections in celiac disease: what should be considered for better management. Clin Exp Med 2024; 25:25. [PMID: 39731690 DOI: 10.1007/s10238-024-01542-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 12/20/2024] [Indexed: 12/30/2024]
Abstract
Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.
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Affiliation(s)
- Nastaran Asri
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahnaz Mohammadi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Jahdkaran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Narciso-Schiavon JL, Schiavon LDL. Hepatitis B and Celiac Disease: a cause for concern? REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:479-485. [DOI: 10.22516/25007440.1016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Some theories suggest that the development of the immune response to clear hepatitis B triggers the intestinal tissue damage seen in celiac disease in genetically predisposed individuals. Although the role of hepatitis B virus infection in the development of autoimmune diseases has been widely discussed in the literature, it remains a controversial topic. Our objective is to review whether there is an association between hepatitis B and celiac disease and the particularities of vaccination against hepatitis B in celiac patients.
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Ibsen JH, Chopra A, Vaage EB, Vaage JT, Lund-Johansen F, Lundin KEA. Immune responses to SARS-CoV-2 vaccines in celiac disease. Scand J Gastroenterol 2023; 58:142-147. [PMID: 36049123 DOI: 10.1080/00365521.2022.2114809] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. METHODS CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. RESULTS Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). CONCLUSION The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.
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Affiliation(s)
- Jostein H Ibsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Adity Chopra
- Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Eline Benno Vaage
- Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - John T Vaage
- Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | | | - Knut E A Lundin
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.,K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Aneja A, Lal SB, Sharma AK, Rawat A, Singh S. Clinical Characteristics of Children With Celiac Disease Not Responding to Hepatitis B Vaccination in India. JPGN REPORTS 2021; 2:e046. [PMID: 37206938 PMCID: PMC10191543 DOI: 10.1097/pg9.0000000000000046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/15/2020] [Indexed: 05/21/2023]
Abstract
The immunological response to hepatitis B virus (HBV) vaccine may be suboptimal in children with celiac disease (CD), but the reasons for this are not well defined. Objectives This study was undertaken to assess the immune response to HBV vaccine in CD children and to explore the possible factors affecting the immune response. Methods The study population consisted of 3 groups-50 newly diagnosed CD children (group 1), 50 previously diagnosed CD children who were on gluten free diet (GFD) >3 months (group 2), and 100 age and gender matched healthy controls (group 3). The patient characteristics were recorded, and the blood samples were analyzed for HBsAg and anti-HBs titers. The nonresponders were given a booster dose of HBV vaccine and reevaluated after 6 weeks. Results Positive anti-HBs response was found in 46% in newly diagnosed CD children, 60% in CD children on GFD, and 83% in healthy controls (P < 0.001). The immune response to HBV vaccine in CD children was inferior to that in healthy children (53% vs 83%, P < 0.001). The immune response was found to be significantly affected by age at diagnosis, delay in diagnosis, type of presentation, and compliance to GFD. 44 out of 45 (97.77%) nonresponders from CD group seroconverted after a single booster dose. Conclusion Early diagnosis and good compliance to GFD may improve the immune response to HBV vaccine in CD children. Single additional booster dose is sufficient to attain optimal immune response.
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Affiliation(s)
- Aradhana Aneja
- From the Division of Paediatric Gastroenterology, Hepatology & Nutrition
| | - Sadhna B. Lal
- From the Division of Paediatric Gastroenterology, Hepatology & Nutrition
| | | | - Amit Rawat
- Division of Paediatric Immunology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Surjit Singh
- Division of Paediatric Immunology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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Passanisi S, Dipasquale V, Romano C. Vaccinations and Immune Response in Celiac Disease. Vaccines (Basel) 2020; 8:278. [PMID: 32517026 PMCID: PMC7349995 DOI: 10.3390/vaccines8020278] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 12/16/2022] Open
Abstract
Immune response to vaccinations in celiac patients is of growing scientific interest. However, some aspects of the relationship between celiac disease (CD) and vaccines are still unclear. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: "adaptive immunity", "celiac disease", "humoral immune response", "immunization", and "vaccination". To date, there is no evidence showing any causative association between vaccines and CD development. Therefore, vaccinations may be administered according to the modalities and timing of the National Immunization Schedule for each country. The rotavirus vaccine is currently recommended for the general population, and according to some data, it appears to reduce the risk for the development of CD autoimmunity in the early years of life. Regarding the hepatitis B virus, a booster dose of the vaccine is often required due to the low or the lost immune response rate in CD. Furthermore, determination of hepatitis B antibody titers could be useful in newly diagnosed CD subjects regardless of age at diagnosis. Finally, pneumococcal vaccines may be administered in patients with advancing age at diagnosis and concomitant risk factors. Future clinical practice guidelines for vaccination and monitoring programs in celiac patients could be recommended.
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Affiliation(s)
| | | | - Claudio Romano
- Paediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (S.P.); (V.D.)
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Hayden CA, Landrock D, Hung CY, Ostroff G, Fake GM, Walker JH, Kier A, Howard JA. Co-Administration of Injected and Oral Vaccine Candidates Elicits Improved Immune Responses over Either Route Alone. Vaccines (Basel) 2020; 8:E37. [PMID: 31973150 PMCID: PMC7157212 DOI: 10.3390/vaccines8010037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 12/22/2022] Open
Abstract
Infectious diseases continue to be a significant cause of morbidity and mortality, and although efficacious vaccines are available for many diseases, some parenteral vaccines elicit little or no mucosal antibodies which can be a significant problem since mucosal tissue is the point of entry for 90% of pathogens. In order to provide protection for both serum and mucosal areas, we have tested a combinatorial approach of both parenteral and oral administration of antigens for diseases caused by a viral pathogen, Hepatitis B, and a fungal pathogen, Coccidioides. We demonstrate that co-administration by the parenteral and oral routes is a useful tool to increase the overall immune response. This can include achieving an immune response in tissues that are not elicited when using only one route of administration, providing a higher level of response that can lead to fewer required doses or possibly providing a better response for individuals that are considered poor or non-responders.
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Affiliation(s)
- Celine A. Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
| | - Danilo Landrock
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, TX 77843, USA; (D.L.); (A.K.)
| | - Chiung Yu Hung
- Department of Biology, University of Texas San Antonio, One UTSA Circle, San Antonio, TX 78249, USA;
| | - Gary Ostroff
- Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St. Biotech 2, Suite 113, Worcester, MA 01605, USA;
| | - Gina M. Fake
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
| | - John H. Walker
- Department of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USA;
| | - Ann Kier
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, TX 77843, USA; (D.L.); (A.K.)
| | - John A. Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
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Abstract
Celiac disease is a common form of enteropathy with frequent extraintestinal manifestations (EIM). Misrecognition of these presentations may lead to significant delays in diagnosis. Any organ may be involved, either through an immune/inflammatory phenomenon, or nutritional deficiencies. Some EIM, such as gluten ataxia, may be irreversible if left untreated, but most will improve with a gluten-free diet. Knowledge of the various EIM, as well as the associated conditions which do not improve on a gluten-free diet, will avoid delays in the diagnosis and management of celiac disease and associated manifestations.
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Affiliation(s)
- Amelie Therrien
- Department of Medicine, Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center
- Celiac Research Program, Harvard Medical School
| | - Ciaran P Kelly
- Department of Medicine, Celiac Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center
- Celiac Research Program, Harvard Medical School
| | - Jocelyn A Silvester
- Celiac Research Program, Harvard Medical School
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children Hospital, Boston, MA
- Rady College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
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Vlasova AN, Takanashi S, Miyazaki A, Rajashekara G, Saif LJ. How the gut microbiome regulates host immune responses to viral vaccines. Curr Opin Virol 2019; 37:16-25. [PMID: 31163292 PMCID: PMC6863389 DOI: 10.1016/j.coviro.2019.05.001] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 04/30/2019] [Accepted: 05/02/2019] [Indexed: 02/07/2023]
Abstract
The co-evolution of the microbiota and immune system has forged a mutually beneficial relationship. This relationship allows the host to maintain the balance between active immunity to pathogens and vaccines and tolerance to self-antigens and food antigens. In children living in low-income and middle-income countries, undernourishment and repetitive gastrointestinal infections are associated with the failure of oral vaccines. Intestinal dysbiosis associated with these environmental influences, as well as some host-related factors, compromises immune responses and negatively impacts vaccine efficacy. To understand how immune responses to viral vaccines can be optimally modulated, mechanistic studies of the relationship between the microbiome, host genetics, viral infections and the development and function of the immune system are needed. We discuss the potential role of the microbiome in modulating vaccine responses in the context of a growing understanding of the relationship between the gastrointestinal microbiota, host related factors (including histo-blood group antigens) and resident immune cell populations.
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Affiliation(s)
- Anastasia N Vlasova
- Food Animal Health Research Program, CFAES, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA.
| | - Sayaka Takanashi
- Food Animal Health Research Program, CFAES, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA; Department of Developmental Medical Sciences, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Ayako Miyazaki
- Division of Viral Disease and Epidemiology, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-0856, Japan
| | - Gireesh Rajashekara
- Food Animal Health Research Program, CFAES, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA
| | - Linda J Saif
- Food Animal Health Research Program, CFAES, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA.
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Abstract
There is substantial variation between individuals in the immune response to vaccination. In this review, we provide an overview of the plethora of studies that have investigated factors that influence humoral and cellular vaccine responses in humans. These include intrinsic host factors (such as age, sex, genetics, and comorbidities), perinatal factors (such as gestational age, birth weight, feeding method, and maternal factors), and extrinsic factors (such as preexisting immunity, microbiota, infections, and antibiotics). Further, environmental factors (such as geographic location, season, family size, and toxins), behavioral factors (such as smoking, alcohol consumption, exercise, and sleep), and nutritional factors (such as body mass index, micronutrients, and enteropathy) also influence how individuals respond to vaccines. Moreover, vaccine factors (such as vaccine type, product, adjuvant, and dose) and administration factors (schedule, site, route, time of vaccination, and coadministered vaccines and other drugs) are also important. An understanding of all these factors and their impacts in the design of vaccine studies and decisions on vaccination schedules offers ways to improve vaccine immunogenicity and efficacy.
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Aboelnaga A, Shaarawy S, Hassabo AG. Polyaconitic acid/functional amine/azo dye composite as a novel hyper-branched polymer for cotton fabric functionalization. Colloids Surf B Biointerfaces 2018; 172:545-554. [PMID: 30216905 DOI: 10.1016/j.colsurfb.2018.09.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 12/01/2022]
Abstract
A new hyperbranched polymer based on aconitic acid and two different amine (triethnaol amine and diethylenetriamine) with different functional groups; hydroxyl and amine groups respectively was successfully synthesised by A2B3 polymerization technique and characterised using Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR), rheological properties, antimicrobial and cytotoxicity activity. In addition, a new heterocyclic azo dye was synthesised and characterised using FT-IR, NMR, mass spectra and antimicrobial activity. Characterisation provides that both composites and azo dye have been well prepared. A mixture from both hyberbranched polymer and synthesised azo dye have been applied to cotton fabrics. Evaluation of treated fabrics shows that, the surface of treated fabrics has a thin film from applied composite which coated the whole fibre surface. Treated fabrics have good antimicrobial activity against gram positive, gram negative bacteria and fungi. Fastness properties, physical and mechanical properties for treated fabrics were also evaluated.
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Affiliation(s)
- Asmaa Aboelnaga
- Faculty of Science, Chemistry Department, Yanbu, Taibah University, Saudi Arabia; Faculty of Women for Arts, Science and Education, Chemistry Department, Ain Shams University, Heliopolis, Cairo, 11757, Egypt
| | - Sahar Shaarawy
- National Research Centre (Scopus affiliation ID 60014618), Textile Industries Research Division, Pre-treatment and Finishing of Cellulosic based Fibre Department, 33-El-Behouth St. (former El-Tahrir str.), Dokki, P.O. 12622, Giza, Egypt
| | - Ahmed G Hassabo
- National Research Centre (Scopus affiliation ID 60014618), Textile Industries Research Division, Pre-treatment and Finishing of Cellulosic based Fibre Department, 33-El-Behouth St. (former El-Tahrir str.), Dokki, P.O. 12622, Giza, Egypt.
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12
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Manti S, Cuppari C, Parisi GF, Tardino L, Salpietro C, Leonardi S. HMGB1 values and response to HBV vaccine in children with celiac disease. Nutrition 2017; 42:20-22. [PMID: 28870474 DOI: 10.1016/j.nut.2017.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 04/30/2017] [Accepted: 05/15/2017] [Indexed: 12/17/2022]
Abstract
OBJECTIVES In addition to its wide clinical variability, celiac disease (CD) can also cause a lower response to the hepatitis B virus (HBV) than healthy individuals. The aim of this study was to examine high mobility group box 1 (HMGB1) as a new potential marker of an inadequate response to HBV vaccine in children with CD at diagnosis before starting a gluten-free diet. METHODS We recruited 49 children with CD who were tested at admission for immunization against HBV. Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay test. RESULTS Serum HMGB1 levels were significantly higher in nonresponders than in responders (P < 0.05). In the responders group in particular, with reference to the titer of vaccine response, we found a significantly higher serum HMGB1 level in the low responders (P < 0.001). We detected statistically significant higher values of HMGB1 in the typical form of disease presentation than in the atypical or silent form (P < 0.05). In the typical form, we showed even significantly higher HMGB1 values in low responders than in high responders (P < 0.001). With regard to the HLA haplotype and serum HMGB1 levels, any statistically significant difference was detected (P > 0.05). CONCLUSIONS In patients with CD, HMGB1 could represent a new marker that is able to reflect the immune impairment that results in failure of the HBV vaccination.
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Affiliation(s)
- Sara Manti
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Giuseppe F Parisi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Lucia Tardino
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Carmelo Salpietro
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
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13
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Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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14
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Filippelli M, Garozzo MT, Capizzi A, Spina M, Manti S, Tardino L, Salpietro C, Leonardi S. Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis. World J Hepatol 2016; 8:1105-1109. [PMID: 27660678 PMCID: PMC5026993 DOI: 10.4254/wjh.v8.i26.1105] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 07/14/2016] [Accepted: 07/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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Affiliation(s)
- Martina Filippelli
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Maria Teresa Garozzo
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Antonino Capizzi
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Massimo Spina
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Sara Manti
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Lucia Tardino
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Carmelo Salpietro
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Salvatore Leonardi
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
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15
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Hepatitis B Virus Revaccination With Standard Versus Pre-S Vaccine in Previously Immunized Patients With Celiac Disease. J Pediatr Gastroenterol Nutr 2015; 61:400-3. [PMID: 25988560 DOI: 10.1097/mpg.0000000000000856] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Previous studies have suggested that hepatitis B virus (HBV) vaccines may be less immunogenic in individuals with celiac disease (CD). A pre-S vaccine (Sci-B-Vac) has demonstrated superior immunogenicity compared with standard HBV vaccines in several diseases. We compared the short-term immunogenicity of a pre-S vaccine with a HBV vaccine (Engerix B) for repeat vaccination of seronegative, previously immunized patients with CD. METHODS Participants were 1 to 18-year-old children with CD who despite standard HBV vaccines in infancy had nonprotective hepatitis B surface antibody (HBs-Ab) concentrations (≤10 mIU/mL). Patients were randomized to receive either Engerix B or pre-S vaccine. HBs-Ab concentrations were measured 1 month after the first dose. For those who had not responded after 1 dose, measurement was repeated after the third dose. RESULTS Children (n = 82) were analyzed (42 pre-S vaccine and 40 Engerix B). Baseline characteristics were similar for both groups, including gluten-free diet status. Both arms showed high response rates following the first injection: 41 (98%) versus 35 (87%) for pre-S vaccine and Engerix B recipients, respectively (P = 0.08). All other patients responded when measured after dose 3. HBs-Ab concentrations (mIU/mL) were higher in the pre-S vaccine group (median 925, interquartile range [IQR] 424-1000) than the Engerix B group (median 363, IQR 106-996, P = 0.005). Twenty (48%) of the pre-S vaccine recipients were "high responders" (>1000 mIU/mL) versus 10 (25%) in Engerix B recipients (P = 0.008). CONCLUSIONS Both vaccines elicited adequate booster responses in most previously vaccinated patients with CD with nonprotective HBs-Ab concentrations. Pre-S vaccine administration resulted in higher Hbs-Ab concentrations. Our data suggest that a single dose of either vaccine is sufficient to raise titers to protective levels in most patients with CD.
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16
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Opri R, Veneri D, Mengoli C, Zanoni G. Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis. Hum Vaccin Immunother 2015; 11:2800-5. [PMID: 26378476 DOI: 10.1080/21645515.2015.1069448] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
It is debated whether patients with celiac disease (CD) have non-protective antibody responses to HBV vaccination more frequently than non-affected subjects. To perform a literature review and meta-analysis on protective response to HBV vaccination in CD patients. RCTs and observational controlled studies were eligible. Outcome of interest was an anti-HBs (HBsAb) titer ≥ 10 IU/L after last vaccine dose. Comparative index was rate ratio (RR). Heterogeneity between studies was addressed and funnel plots were analyzed. Meta-regression models were applied to investigate effect size due to study-specific variables. Twelve retrospective studies on a total of 1,447 participants and 4 prospective studies on 184 subjects were selected. The RR was 0.732 (95% C.I.: 0.664-0.808) and 0.777 (95% C.I.: 0.629-0.960) in the prospective and retrospective studies, respectively. The I(2), indicating heterogeneity, was 51.1% in retrospective, 39.8% in prospective studies. Non-protective antibody responses occurred more frequently in patients than controls. Due to limitations in the available studies, additional trials to evaluate post-vaccination HBsAb titer in CD patients are needed.
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Affiliation(s)
- R Opri
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
| | - D Veneri
- b Department of Medicine ; Section of Hematology; University of Verona ; Verona , Italy
| | - C Mengoli
- c Infectious Diseases; University of Padua ; Padua , Italy
| | - G Zanoni
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
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17
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Filippelli M, Lionetti E, Pulvirenti A, Gennaro A, Lanzafame A, Marseglia GL, Salpietro C, Rosa ML, Leonardi S. New approaches in hepatitis B vaccination for celiac disease. Immunotherapy 2015; 6:945-52. [PMID: 25313572 DOI: 10.2217/imt.14.64] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CD) is a gluten-induced immune-mediated disorder that has been associated with a defective response to the hepatitis B virus (HBV) vaccination. This unresponsiveness could lead to a world health problem, because non-responder patients could represent a reservoir of HBV-susceptible people that will persist as healthy carriers, leading to the diffusion of the disease. This article presents a literature review of both intramuscular (IM) and intradermal (ID) routes for boosters in celiac patients. We used PubMed database and generated the odds ratio (OR) of the response on the basis of electronic searches of clinical trials. Although our results confirm the positive response of celiac patients to IM vaccination, the ID route seems to be better than the conventional one, since it could provide a saving in cost and a greater immunogenicity.
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Affiliation(s)
- Martina Filippelli
- Department of Medical & Pediatric Science, University of Catania, Catania, Italy
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18
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Jamieson AM. Influence of the microbiome on response to vaccination. Hum Vaccin Immunother 2015; 11:2329-31. [PMID: 26090701 PMCID: PMC4635895 DOI: 10.1080/21645515.2015.1022699] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 02/19/2015] [Indexed: 12/18/2022] Open
Abstract
In order for vaccines to be effective within a given population not only do large numbers of people need to be vaccinated, but a large proportion of those vaccinated must develop protective immunity. The mechanisms that lead to a poor immune response to vaccination are complex and poorly understood, but include both genetic and environmental factors. The bacteria that exist throughout the human body, known as the microbiome, play a variety of roles in the development of the immune system. This is particularly true during infancy when the microbiome and the immune response are developing in tandem. Most vaccines are administered in early childhood to prevent outbreaks of devastating childhood diseases. Understanding the impact that the early microbiome plays in response to vaccination will improve our understanding of vaccine efficacy.
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Affiliation(s)
- Amanda M Jamieson
- Department of Molecular Microbiology and Immunology; Brown University; Providence, RI USA
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19
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Walkiewicz-Jedrzejczak D, Egberg M, Nelson C, Eickoff J. Evaluation of the response to vaccination with hepatitis B vaccine in pediatric patients diagnosed with celiac disease. SAGE Open Med 2014; 2:2050312114563346. [PMID: 26770758 PMCID: PMC4607240 DOI: 10.1177/2050312114563346] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 11/11/2014] [Indexed: 12/28/2022] Open
Abstract
Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination. Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine. Design/Methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables were summarized by means, standard deviations, medians, and ranges. A two-sample t-test was used to compare normally distributed continuous variables between responders and non-responders. Results: In all, 58% of patients did not meet the threshold for “protective” antibody titers. The mean time between completion of hepatitis B vaccination and diagnosis of celiac disease was 8.1 years for responders versus 10.5 years for non-responders. In a multivariate analysis, time between completion of vaccine and diagnosis of celiac disease was statistically significant predictor of response with an adjusted odds ratio of 0.69 (95% confidence interval: 0.50–0.95; p = 0.021). Conclusion: Our celiac disease population shows a high hepatitis B vaccine failure. The time between completion of vaccine series and diagnosis of celiac disease is an independent predictor for response.
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Affiliation(s)
| | - Matthew Egberg
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Catherine Nelson
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jens Eickoff
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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20
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Hayden CA, Smith EM, Turner DD, Keener TK, Wong JC, Walker JH, Tizard IR, Jimenez-Flores R, Howard JA. Supercritical fluid extraction provides an enhancement to the immune response for orally-delivered hepatitis B surface antigen. Vaccine 2014; 32:1240-6. [PMID: 24486361 DOI: 10.1016/j.vaccine.2014.01.037] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 12/27/2013] [Accepted: 01/14/2014] [Indexed: 01/27/2023]
Abstract
The hepatitis B virus continues to be a major pathogen worldwide despite the availability of an effective parenteral vaccine for over 20 years. Orally-delivered subunit vaccines produced in maize may help to alleviate the disease burden by providing a low-cost, heat-stable alternative to the parenteral vaccine. Oral subunit vaccination has been an elusive goal due to the large amounts of antigen required to induce an immunologic response when administered through the digestive tract. Here we show that high levels of HBsAg were obtained in maize grain, the grain was formed into edible wafers, and wafers were fed to mice at a concentration of approximately 300 μg/g. When these wafers were made with supercritical fluid extraction (SFE)-treated maize material, robust IgG and IgA responses in sera were observed that were comparable to the injected commercial vaccine (Recombivax(®)). In addition, all mice administered SFE wafers showed high secretory IgA titers in fecal material whereas Recombivax(®) treated mice showed no detectable titer. Increased salivary IgA titers were also detected in SFE-fed mice but not in Recombivax(®) treated mice. Wafers made from hexane-treated or full fat maize material induced immunologic responses, but fecal titers were attenuated relative to those produced by SFE-treated wafers. These responses demonstrate the feasibility of using a two-dose oral vaccine booster in the absence of an adjuvant to induce immunologic responses in both sera and at mucosal surfaces, and highlight the potential limitations of using an exclusively parenteral dosing regime.
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Affiliation(s)
- Celine A Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Emily M Smith
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Debra D Turner
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
| | - Todd K Keener
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Jeffrey C Wong
- Horticulture and Crop Science Department, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - John H Walker
- Department of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - Ian R Tizard
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
| | - Rafael Jimenez-Flores
- Dairy Product Technology Center, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - John A Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
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21
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Zingone F, Capone P, Tortora R, Rispo A, Morisco F, Caporaso N, Imperatore N, De Stefano G, Iovino P, Ciacci C. Role of gluten intake at the time of hepatitis B virus vaccination in the immune response of celiac patients. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2013; 20:660-662. [PMID: 23446217 PMCID: PMC3647759 DOI: 10.1128/cvi.00729-12] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 02/19/2013] [Indexed: 02/07/2023]
Abstract
Some reports have demonstrated an inadequate response to hepatitis B vaccination in patients affected by celiac disease. The aim of our study was to evaluate hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease. To measure the gluten exposure status at the time of vaccination, we considered three groups: group A (exposed to gluten), including patients vaccinated as 12-year-old adolescents (the celiac disease diagnosis was established after vaccination); group B (not exposed to gluten), including patients vaccinated as 12-year-old adolescents on a gluten-free diet at the time of vaccination; and group C (infants), including patients vaccinated at birth. The response of celiac patients to hepatitis B vaccination was compared to that of healthy subjects, i.e., those in the control group (group D). This study included 163 celiac patients (group A, 57 patients; group B, 46 patients; and group C, 60 patients) and 48 controls (group D). An inadequate response to hepatitis B immunization was present in 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D (group A versus group D, P < 0.001; group B versus group D, P = 0.002; group C versus group D, P = 0.001) (no significant difference for group A versus group B and group A versus group C was evident). Our data suggest that gluten exposure does not influence the response to hepatitis B immunization and that the human leukocyte antigen probably plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients.
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Affiliation(s)
- F. Zingone
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - P. Capone
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - R. Tortora
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - A. Rispo
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - F. Morisco
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - N. Caporaso
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - N. Imperatore
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - G. De Stefano
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - P. Iovino
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - C. Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
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22
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Urganci N, Kalyoncu D. Response to hepatitis A and B vaccination in pediatric patients with celiac disease. J Pediatr Gastroenterol Nutr 2013; 56:408-11. [PMID: 23132166 DOI: 10.1097/mpg.0b013e31827af200] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES The aim of the study was to evaluate the response to hepatitis A and B vaccinations in pediatric patients with celiac disease (CD). METHODS Thirty patients with CD ages 1 to 15 years were compared with 50 healthy age-, sex-, and body mass index-matched controls. Screening for hepatitis A and B serology was carried out before vaccination. Susceptible cases received 20 μg of recombinant DNA vaccine for hepatitis B (0,1, and 6 months) and 720 milliELISA units of inactivated hepatitis A virus (HAV) vaccine (0 and 6 months). Postvaccination serologic evaluation was performed 1 month after the last dose of primary vaccination, 1 month after the booster dose, and once every year during follow-up. RESULTS Sixteen patients and 35 controls received hepatitis A vaccine; protective anti-HAV antibodies were developed in 12 (75%) of the patients and all of the controls (75% vs 100%, respectively; 95% confidence interval [CI] 0.47-0.92, P=0.007). Thirty patients and 50 controls received hepatitis B vaccine, and 70% of the patients vs 90% of the controls achieved seroprotection (anti-HBs titers ≥10 mIU/mL) 1 month after primary vaccination (95% CI 0.74-0.90, P=0.03). Four patients were unresponsive to both of the vaccines. The overall seroprotection rates were 96% in controls and 80% in patients after the whole hepatitis B vaccination series (95% CI 0.04-0.18, P=0.04). No significant reduction was observed in antibody response among patients and controls during follow-up period. CONCLUSIONS The rate of seroconversion to the hepatitis B virus- and HAV vaccine is lower in patients with CD than in healthy controls.
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Affiliation(s)
- Nafiye Urganci
- Division of Pediatric Gastroenterology, Department of Pediatrics, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
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23
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Vitaliti G, Praticò AD, Cimino C, Di Dio G, Lionetti E, La Rosa M, Leonardi S. Hepatitis B vaccine in celiac disease: Yesterday, today and tomorrow. World J Gastroenterol 2013; 19:838-45. [PMID: 23430309 PMCID: PMC3574880 DOI: 10.3748/wjg.v19.i6.838] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 10/12/2012] [Accepted: 10/16/2012] [Indexed: 02/06/2023] Open
Abstract
Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.
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24
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Schillie SF, Spradling PR, Murphy TV. Immune response of hepatitis B vaccine among persons with diabetes: a systematic review of the literature. Diabetes Care 2012; 35:2690-7. [PMID: 23173138 PMCID: PMC3507602 DOI: 10.2337/dc12-0312] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Sarah F Schillie
- Division of Viral Hepatitis, Vaccine Research and Policy Team, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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25
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Leonardi S, Praticò AD, Lionetti E, Spina M, Vitaliti G, Rosa ML. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children. World J Gastroenterol 2012; 18:5729-33. [PMID: 23155313 PMCID: PMC3484341 DOI: 10.3748/wjg.v18.i40.5729] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Revised: 07/16/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals.
METHODS: We conducted our study on 58 celiac patients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepatitis B virus (HBV) antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine (Engerix B) 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low responders" while patients with an antibody titer higher than 1000 IU/L were considered "high responders".
RESULTS: No significant difference in age, gender, duration of illness, and years of gluten intake was found between the two groups. We found a high percentage of "responders" after the first booster dose (ID = 76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM = 96.4%) of vaccine in both groups. Moreover we found a significantly higher number of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%) than in the IM (7.1%) group, and this difference was evident after the first booster dose of vaccination (P < 0.01). No side effects were recorded in performing delivery of the vaccine by either the ID or IM route.
CONCLUSION: Our study suggests that both ID and IM routes are effective and safe options to administer a booster dose of HBV vaccine in celiac patients. However the ID route seems to achieve a greater number of high responders and to have a better cost/benefit ratio.
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26
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Hayden CA, Egelkrout EM, Moscoso AM, Enrique C, Keener TK, Jimenez-Flores R, Wong JC, Howard JA. Production of highly concentrated, heat-stable hepatitis B surface antigen in maize. PLANT BIOTECHNOLOGY JOURNAL 2012; 10:979-84. [PMID: 22816734 PMCID: PMC3517206 DOI: 10.1111/j.1467-7652.2012.00727.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Plant-based oral vaccines are a promising emergent technology that could help alleviate disease burden worldwide by providing a low-cost, heat-stable, oral alternative to parenterally administered commercial vaccines. Here, we describe high-level accumulation of the hepatitis B surface antigen (HBsAg) at a mean concentration of 0.51%TSP in maize T1 seeds using an improved version of the globulin1 promoter. This concentration is more than fourfold higher than any previously reported lines. HBsAg expressed in maize seeds was extremely heat stable, tolerating temperatures up to 55 °C for 1 month without degradation. Optimal heat stability was achieved after oil extraction of ground maize material, either by supercritical fluid extraction or hexane treatment. The contributions of this material towards the development of a practical oral vaccine delivery system are discussed.
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Affiliation(s)
- Celine A. Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Erin M. Egelkrout
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Alessa M. Moscoso
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Cristina Enrique
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Todd K. Keener
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Rafael Jimenez-Flores
- Dairy Science Department, California Polytechnic State University, San Luis Obispo, CA 93407
| | - Jeffrey C. Wong
- Horticulture and Crop Science Department, California Polytechnic State University, San Luis Obispo, CA 93407
| | - John A. Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
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27
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Hayden CA, Streatfield SJ, Lamphear BJ, Fake GM, Keener TK, Walker JH, Clements JD, Turner DD, Tizard IR, Howard JA. Bioencapsulation of the hepatitis B surface antigen and its use as an effective oral immunogen. Vaccine 2012; 30:2937-42. [PMID: 22406456 DOI: 10.1016/j.vaccine.2012.02.072] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 02/05/2012] [Accepted: 02/25/2012] [Indexed: 01/14/2023]
Abstract
Hepatitis B remains a major global health problem despite the availability of a safe and effective vaccine. Segments of the population lack access to or respond poorly to the parenteral vaccine, perpetuating the infection-transmission cycle. A low cost, orally delivered vaccine has the potential to alleviate many of these problems. Here we describe the expression of a bioencapsulated hepatitis B surface antigen (HBsAg) in maize and its immunogenicity, demonstrating for the first time a commercially feasible oral subunit vaccine production system for a major disease. This work surmounts previous barriers to plant-produced vaccines by expressing HBsAg at much higher levels and retaining antigen immunogenicity post-processing: factors which facilitated a robust immune response in mice without the need for an adjuvant. This method provides a practical solution to the delivery of a low-cost, stable oral vaccine.
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Affiliation(s)
- Celine A Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, United States
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Abstract
OBJECTIVES The response to hepatitis A vaccine has not been studied in children with celiac disease (CD). The aim of the present study was to evaluate the immunogenicity of an inactivated hepatitis A virus (HAV) vaccine and the effect of the human leukocyte antigen (HLA) type on immunogenicity in children with CD. PATIENTS AND METHODS Thirty-three patients with CD and 62 healthy controls were enrolled in the study. Inactivated HAV vaccine (Havrix; GlaxoSmithKline Biologicals, Rixensart, Belgium) containing 720 enzyme-linked immunosorbent assay units of alum-adsorbed hepatitis A antigen was administered intramuscularly in a 2-dose schedule at 0 and 6 months. Seroconversion rates and antibody titers of HAV were measured at 1 and 7 months. RESULTS At 1 month, seroconversion rates were 78.8% and 77.4% and geometric mean titers were 50.7 and 49.9 mIU/mL in the CD and control groups, respectively (P > 0.05). At 7 months, seroconversion rates were 97% and 98.4% and geometric mean titers were 138.5 and 133 mIU/mL in the CD and control groups, respectively (P > 0.05). The most frequent HLA types were HLA-DQ2, -DR3, and -DR7 alleles in patients with CD and HLA-DQ3, -DQ6, -DR11, and -DR14 in the controls. There was no association between HLA alleles and antibody titers of hepatitis A vaccine. CONCLUSION Children with CD have a good immune response to hepatitis A vaccine, similar to healthy controls.
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New Hepatitis B Vaccine Schedule for Children with Celiac Disease. HEPATITIS MONTHLY 2011. [DOI: 10.5812/kowsar.1735143x.1105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Ertekin V, Tosun MS, Selimoglu MA. Is there need for a new hepatitıs B vaccine schedule for children with celiac disease? HEPATITIS MONTHLY 2011. [PMID: 22140387 DOI: 10.5812/kowsar.1735143x.1129] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Celiac disease (CD) is an autoimmune disease characterized by immunemediated inflammatory damage of the small intestinal mucosa, precipitated by the ingestion of gluten-containing foods. Since human leucocyte antigen DQ2 (HLA-DQ2) is a marker of nonresponsiveness to hepatits B virus (HBV) vaccine, CD may also be associated with this nonresponsiveness. OBJECTIVES The aim of this study was to compare the responses to HBV vaccine between children with CD and healthy children. We also investigated the relationship between the patients' responses to hepatitis B vaccine, the clinical presentation of CD, and dietary compliance in the patients. PATIENTS AND METHODS We recruited 52 children with CD and 20 age- and sex-matched healthy children who received HBV vaccination according to the standard immunization schedule. The production of specific antihepatitis B surface antigen (HBsAg) antibodies was evaluated in all patients and control participants. Subjects with less than 10 IU/L anti-HBs were consided nonresponders to the vaccination. RESULTS 31 of the 52 patients (59.6%) were female and 21 (40.4%) were male. The mean age of the CD patients was 10.7 ± 4 years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05). We found statistically significant differences between negative anti-HBs titers, clinical presentation of CD, and dietary compliance in patients with CD (P < 0.05). CONCLUSIONS Nonresponsiveness to hepatitis B vaccination was more frequently found in children with CD than in the control group. Therefore, the response to HBV vaccination should be investigated in children with CD, and a different immunization schedule may need to be developed. Further, compliance to the prescribed gluten-free diet (GFD) may improve the immune response to HBV vaccination in children with CD.
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Affiliation(s)
- Vildan Ertekin
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul Faculty of Medical Sciences, Istanbul University, Istanbul, Turkey
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Gisbert JP, Chaparro M, Esteve M. Review article: prevention and management of hepatitis B and C infection in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33:619-33. [PMID: 21416659 DOI: 10.1111/j.1365-2036.2010.04570.x] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Viral hepatitis is a very common infection. AIM To review the prevention and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in inflammatory bowel disease (IBD). METHODS Bibliographical searches were performed in MEDLINE up to September 2010. RESULTS The prevalence of both HBV and HCV infection in IBD patients is now similar to that of the general population. All IBD patients should be screened for HBV markers at diagnosis. Liver dysfunction in IBD patients treated with immunosuppressants is more frequent and severe in HBV than in HCV carriers and is associated with combined immunosuppression. Inpatients receiving anti-TNF drugs, HBV reactivation is common unless anti-viral prophylaxis is administered. HBsAg-positive patients should receive anti-viral prophylaxis before starting immunosuppressants. As interferon might worsen underlying IBD, nucleoside ⁄ nucleotide analogues are preferred for anti-viral prophylaxis in patients with HBV (tenofovir ⁄ entecavir are preferred to lamivudine). IBD patients should be vaccinated against HBV at diagnosis. The response rate to HBV vaccination is low, mainly in those receiving anti-TNF therapy. The serological response to HBV vaccine should be confirmed, and patients with an inadequate response should receive a second full series of vaccine. Peginterferon (ribavirin) for HCV infection is as effective and safe as in non-IBD patients. CONCLUSIONS The present manuscript poses a series of questions on the prevention and management of HBV/HCV infection in IBD, and attempts to answer them using scientific evidence in order to provide practical conclusions for the clinician.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria, Princesa (IP), Madrid, Spain.
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Leonardi S, Vitaliti G, Pratico’ A, Pecoraro R, Rosa ML. A Retrospective Study on Standard Regimen for Vaccination in Celiac Children. ACTA ACUST UNITED AC 2011. [DOI: 10.4236/wjv.2011.12006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Role of HLA allele polymorphism in chronic hepatitis B virus infection and HBV vaccine sensitivity in patients from eastern Turkey. Biochem Genet 2010; 49:258-69. [PMID: 21188498 DOI: 10.1007/s10528-010-9404-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2010] [Accepted: 10/04/2010] [Indexed: 12/20/2022]
Abstract
Human leukocyte antigen (HLA) alleles have been associated with the clinical outcomes of hepatitis B virus (HBV) infection, which range from spontaneous recovery to hepatocellular carcinoma. In this study involving subjects from eastern Turkey, the frequencies of HLA-B35, HLA-CW4, HLA-DQ2, and HLA-DQ8 were markedly higher in the chronic HBV group than those in the spontaneously recovered group; the frequencies of HLA-A11 and HLA-A24 in the nonresponsive HBV vaccine group were markedly higher than those in the responsive HBV vaccine group; and the frequency of HLA-CW6 in the nonresponsive HBV vaccine group was significantly lower than in the responsive group. A complete understanding of HLA types associated with the progression to chronic HBV infection and their effects within the cell at the molecular level will be an important contribution in the development of new HBV vaccines and new treatment strategies for chronic HBV infection.
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Zingone F, Morisco F, Zanetti A, Romanò L, Portella G, Capone P, Andreozzi P, Tortora R, Ciacci C. Long-term antibody persistence and immune memory to hepatitis B virus in adult celiac patients vaccinated as adolescents. Vaccine 2010; 29:1005-8. [PMID: 21129395 DOI: 10.1016/j.vaccine.2010.11.060] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 11/09/2010] [Accepted: 11/16/2010] [Indexed: 12/21/2022]
Abstract
Aim of this study was to investigate the anti-HBs antibody persistence and immune memory to hepatitis B virus in adult celiacs vaccinated as adolescents and the effect of a booster administration in non-protected individuals. Eleven years after primary vaccination, the proportion of vaccinees with titres ≥ 10 mIU/ml and antibody geometric mean concentrations (GMCs) were lower among celiac patients than among controls (68.6% vs 91.7%, p<0.01; GMCs 29.38 mIU/ml vs 250.6 mIU/ml, p<0.001). Participants with anti-HBs below 10 mIU/ml received a booster dose and were retested 2 weeks later to assess the anamnestic response. Post-booster anti-HBs levels were still <10 mIU/ml in 71.4% celiacs and 25% controls (p<0.01). Our findings indicate that the prevalence of seroprotective levels of anti-HBs detected eleven years after primary immunization as well as the frequency of response to a booster dose of vaccine are lower in celiac patients compared to healthy controls.
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Affiliation(s)
- F Zingone
- Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy
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Mårild K, Fredlund H, Ludvigsson JF. Increased risk of hospital admission for influenza in patients with celiac disease: a nationwide cohort study in Sweden. Am J Gastroenterol 2010; 105:2465-73. [PMID: 20823839 DOI: 10.1038/ajg.2010.352] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Although earlier studies suggest an increased risk of infectious disease in celiac disease (CD), data on the risk of influenza in patients with CD are limited. We examined the risk of hospital admission for influenza in CD patients, but for comparative reasons also in individuals with small-intestinal inflammation or normal mucosa but positive CD serology. METHODS In 2006-2008, we collected duodenal/jejunal biopsy data on CD (Marsh 3: villous atrophy, VA; n=29,008 unique individuals) and inflammation (Marsh 1-2; n=13,200) from all 28 pathology departments in Sweden. A third regional cohort consisted of 3,709 individuals with positive CD serology but normal mucosa (Marsh 0). The biopsies were performed between 1969 and 2008. Through linkage with the Swedish Hospital Discharge Register, we estimated the risk of hospital admission for influenza compared with that of 224,114 age- and sex-matched controls from the general population. RESULTS Individuals with CD were at increased risk of hospital admission for influenza (hazard ratio (HR)=2.1; 95% confidence interval (CI)=1.6-2.7; n=81). The absolute risk of influenza was 30/100,000 person-years (excess risk: 16/100,000 person-years). Furthermore, children with CD were at increased risk of influenza (HR=2.5; 95% CI=1.3-4.8). Whereas individuals with inflammation without VA were also at increased risk of influenza (HR=1.9; 95% CI=1.4-2.5), individuals with normal mucosa but positive CD serology were not (HR=1.2; 95% CI=0.5-3.0). CONCLUSIONS This study found an increased risk of hospital admission for influenza in patients with CD.
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Affiliation(s)
- Karl Mårild
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Solna, Sweden.
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Hepatitis B vaccine administered by intradermal route in patients with celiac disease unresponsive to the intramuscular vaccination schedule: a pilot study. Am J Gastroenterol 2010; 105:2117-9. [PMID: 20818367 DOI: 10.1038/ajg.2010.195] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Leonardi S, Spina M, Spicuzza L, Rotolo N, La Rosa M. Hepatitis B vaccination failure in celiac disease: Is there a need to reassess current immunization strategies? Vaccine 2009; 27:6030-3. [DOI: 10.1016/j.vaccine.2009.07.099] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2009] [Revised: 07/11/2009] [Accepted: 07/22/2009] [Indexed: 12/14/2022]
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