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Al-Eitan LN, ElMotasem MFM, Khair IY, Alahmad SZ. Vaccinomics: Paving the Way for Personalized Immunization. Curr Pharm Des 2024; 30:1031-1047. [PMID: 38898820 DOI: 10.2174/0113816128280417231204085137] [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: 09/02/2023] [Accepted: 11/15/2023] [Indexed: 06/21/2024]
Abstract
Vaccines are one of the most important medical advancements in human history. They have been successfully used to control and limit the spread of many of the lethal diseases that have plagued us, such as smallpox and polio. Previous vaccine design methodologies were based on the model of "isolate-inactivateinject", which amounts to giving the same vaccine dose to everyone susceptible to infection. In recent years, the importance of how the host genetic background alters vaccine response necessitated the introduction of vaccinomics, which is aimed at studying the variability of vaccine efficacy by associating genetic variability and immune response to vaccination. Despite the rapid developments in variant screening, data obtained from association studies is often inconclusive and cannot be used to guide the new generation of vaccines. This review aims to compile the polymorphisms in HLA and immune system genes and examine the link with their immune response to vaccination. The compiled data can be used to guide the development of new strategies for vaccination for vulnerable groups. Overall, the highly polymorphic HLA locus had the highest correlation with vaccine response variability for most of the studied vaccines, and it was linked to variation in multiple stages of the immune response to the vaccines for both humoral and cellular immunity. Designing new vaccine technologies and immunization regiments to accommodate for this variability is an important step for reaching a vaccinomics-based approach to vaccination.
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Affiliation(s)
- Laith Naser Al-Eitan
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Moh'd Fahmi Munib ElMotasem
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Iliya Yacoub Khair
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Saif Zuhair Alahmad
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan
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Silvestri F, Tromba V, Mazzotta I, Costantino F. How does diabetes type 1 affects immune response to hepatitis B virus vaccine in pediatric population? Evaluation of a booster dose in unresponsive subjects with type 1 diabetes. Minerva Pediatr (Torino) 2023; 75:822-827. [PMID: 31729208 DOI: 10.23736/s2724-5276.19.05678-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) vaccine reduced the incidence of Hepatitis B worldwide. Genetic variability, by the presence of specific haplotypes of HLA system (HLA-DR3, HLA-DR4), influences the response to the vaccination. Subjects affected by type 1 diabetes (T1D), contrary to non-diabetics, have a high prevalence of Hepatitis B. METHODS The objective of the study was to evaluate anti-HBs antigen (anti-HBsAg) antibody (Ab) in a group of 201 children (age range: 2-18 years), regularly vaccinated against HBV according to the national vaccination schedule. Patients with anti-HBs Ab≥10 mIU/mL have been defined "responders" and those with anti-HBs Ab<10mIU/mL have been defined "non-responders." The possible association between the T1D and a low immune response to the vaccine has been subsequently valued. Besides the presence of T1D, other possible influential variables have been studied: sex, age, presence of celiac disease and Hashimoto's thyroiditis, intervening years from the diagnosis of diabetes and presence/absence of diabetic ketoacidosis at time of diagnosis. RESULTS Among the 201 subjects with T1D, 90 (44.8%) were responders, while 111 (55.2%) were non-responders; among the 145 subjects without T1D, 86 (59.3%) were responders and 59 (40.7%) non-responders. We invited "Subjects with T1D non-responders" to undergo a booster dose of the same vaccine. Of these, 21 refused the booster, reducing the sample to 90 patients. After 4 weeks from the booster dose 81 patients showed seroconversion ("false non-responders"), and 9 did not ("true non-responders"). CONCLUSIONS After the booster dose, immune response in our cross-section has been similar to general population. Given the high frequency of "false non-responders" anti-HBsAg Ab should be tested in T1D patients and a booster dose should be administrated in non-responders.
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Affiliation(s)
| | - Valeria Tromba
- Department of Pediatrics, Sapienza University, Rome, Italy
| | - Ines Mazzotta
- Department of Pediatrics, Sapienza University, Rome, Italy
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Dudley MZ, Gerber JE, Budigan Ni H, Blunt M, Holroyd TA, Carleton BC, Poland GA, Salmon DA. Vaccinomics: A scoping review. Vaccine 2023; 41:2357-2367. [PMID: 36803903 PMCID: PMC10065969 DOI: 10.1016/j.vaccine.2023.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 12/24/2022] [Accepted: 02/03/2023] [Indexed: 02/21/2023]
Abstract
BACKGROUND This scoping review summarizes a key aspect of vaccinomics by collating known associations between heterogeneity in human genetics and vaccine immunogenicity and safety. METHODS We searched PubMed for articles in English using terms covering vaccines routinely recommended to the general US population, their effects, and genetics/genomics. Included studies were controlled and demonstrated statistically significant associations with vaccine immunogenicity or safety. Studies of Pandemrix®, an influenza vaccine previously used in Europe, were also included, due to its widely publicized genetically mediated association with narcolepsy. FINDINGS Of the 2,300 articles manually screened, 214 were included for data extraction. Six included articles examined genetic influences on vaccine safety; the rest examined vaccine immunogenicity. Hepatitis B vaccine immunogenicity was reported in 92 articles and associated with 277 genetic determinants across 117 genes. Thirty-three articles identified 291 genetic determinants across 118 genes associated with measles vaccine immunogenicity, 22 articles identified 311 genetic determinants across 110 genes associated with rubella vaccine immunogenicity, and 25 articles identified 48 genetic determinants across 34 genes associated with influenza vaccine immunogenicity. Other vaccines had fewer than 10 studies each identifying genetic determinants of their immunogenicity. Genetic associations were reported with 4 adverse events following influenza vaccination (narcolepsy, GBS, GCA/PMR, high temperature) and 2 adverse events following measles vaccination (fever, febrile seizure). CONCLUSION This scoping review identified numerous genetic associations with vaccine immunogenicity and several genetic associations with vaccine safety. Most associations were only reported in one study. This illustrates both the potential of and need for investment in vaccinomics. Current research in this field is focused on systems and genetic-based studies designed to identify risk signatures for serious vaccine reactions or diminished vaccine immunogenicity. Such research could bolster our ability to develop safer and more effective vaccines.
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Affiliation(s)
- Matthew Z Dudley
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Institute for Vaccine Safety, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
| | - Jennifer E Gerber
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Survey Research Division, RTI International, Washington, DC, USA
| | - Haley Budigan Ni
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Office of Health Equity, California Department of Public Health, Richmond, CA, USA
| | - Madeleine Blunt
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Taylor A Holroyd
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; International Vaccine Access Center, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Bruce C Carleton
- Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Pharmaceutical Outcomes Programme, BC Children's Hospital, Vancouver, BC, Canada; BC Children's Hospital Research Institute, Vancouver, BC, Canada
| | - Gregory A Poland
- Division of General Internal Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN, USA
| | - Daniel A Salmon
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Institute for Vaccine Safety, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA; Department of Health, Behavior & Society, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
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Hernández-Doño S, Sánchez-González RA, Trujillo-Vizuet MG, Zamudio-Castellanos FY, García-Silva R, Bulos-Rodríguez P, Vazquez-Guzmán CA, Cárdenas-Ramos X, de León Rodríguez D, Elías F, Domínguez-Arevillaga S, Pérez-Tirado JM, Vera-Lastra OL, Granados J, Sepúlveda-Delgado J. Protective HLA alleles against severe COVID-19: HLA-A*68 as an ancestral protection allele in Tapachula-Chiapas, Mexico. Clin Immunol 2022; 238:108990. [PMID: 35395388 PMCID: PMC8982524 DOI: 10.1016/j.clim.2022.108990] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 02/13/2022] [Accepted: 03/25/2022] [Indexed: 11/03/2022]
Abstract
HLA is a polymorphic antigen presenter which has provided valuable information on the susceptibility of populations to viruses. Therefore, the study of HLA can reveal specific susceptibility or resistance alleles to severe COVID-19 in an ethnically dependent manner. This pilot study investigated HLA alleles associated with COVID-19 severity in Tapachula, Chiapas, Mexico. A total of 146 Mexican Mestizos were typed for HLA class I and II using PCR-SSP. The patients were classified according to the outcome (death or improvement) and the infection's severity (mild or severe). In addition, a group of exposed uninfected individuals was included. HLA-A*68 was found to be a protective allele against the severe infection and fatal outcome; pC = 0.03, OR = 0.4, 95% CI =0.20-0.86, and pC =0.009, OR = 0.3, 95% CI =0.13-0.71 respectively. HLA-DRB1*03 also appears to be a protective factor against fatal outcome pC = 0.009, OR = 0.1, 95%IC = 0.01-0.66; however, the low frequency of this allele in the studied population limits the statistical power. The severity and fatal outcome of COVID-19 patients in Tapachula, Chiapas depend more on the lack of resistance than susceptibility HLA alleles.
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Affiliation(s)
- Susana Hernández-Doño
- Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Rafael García-Silva
- Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Pedro Bulos-Rodríguez
- Department of Internal Medicine, Hospital Regional de Alta Especialidad Ciudad Salud, Tapachula, Chiapas, Mexico
| | - Carlos A Vazquez-Guzmán
- Department of Internal Medicine, Hospital Regional de Alta Especialidad Ciudad Salud, Tapachula, Chiapas, Mexico
| | | | - Diana de León Rodríguez
- Facultad de Medicina Humana Campus IV, Universidad Autónoma de Chiapas, Mexico; Becario de la Dirección General de Calidad y Educación en Salud, Secretaría de Salud, Mexico
| | - Fabiola Elías
- Facultad de Medicina Humana Campus IV, Universidad Autónoma de Chiapas, Mexico
| | | | | | - Olga Lidia Vera-Lastra
- Department of Internal Medicine, Hospital de Especialidades, Centro Médico la Raza, Chile
| | - Julio Granados
- Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesús Sepúlveda-Delgado
- Research Division, Hospital Regional de Alta Especialidad Ciudad Salud, Tapachula, Chiapas, Mexico.
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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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Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children. Vaccines (Basel) 2021; 9:vaccines9020101. [PMID: 33525661 PMCID: PMC7912643 DOI: 10.3390/vaccines9020101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 11/17/2022] Open
Abstract
Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.
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Hung SC, Hou T, Jiang W, Wang N, Qiao SW, Chow IT, Liu X, van der Burg SH, Koelle DM, Kwok WW, Sollid LM, Mellins ED. Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense. THE JOURNAL OF IMMUNOLOGY 2019; 202:2558-2569. [PMID: 30926644 DOI: 10.4049/jimmunol.1801454] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 03/01/2019] [Indexed: 01/28/2023]
Abstract
We have reported that the major histocompatibility molecule HLA-DQ2 (DQA1*05:01/DQB1*02:01) (DQ2) is relatively resistant to HLA-DM (DM), a peptide exchange catalyst for MHC class II. In this study, we analyzed the role of DQ2/DM interaction in the generation of DQ2-restricted gliadin epitopes, relevant to celiac disease, or DQ2-restricted viral epitopes, relevant to host defense. We used paired human APC, differing in DM expression (DMnull versus DMhigh) or differing by expression of wild-type DQ2, versus a DM-susceptible, DQ2 point mutant DQ2α+53G. The APC pairs were compared for their ability to stimulate human CD4+ T cell clones. Despite higher DQ2 levels, DMhigh APC attenuated T cell responses compared with DMnull APC after intracellular generation of four tested gliadin epitopes. DMhigh APC expressing the DQ2α+53G mutant further suppressed these gliadin-mediated responses. The gliadin epitopes were found to have moderate affinity for DQ2, and even lower affinity for the DQ2 mutant, consistent with DM suppression of their presentation. In contrast, DMhigh APC significantly promoted the presentation of DQ2-restricted epitopes derived intracellularly from inactivated HSV type 2, influenza hemagglutinin, and human papillomavirus E7 protein. When extracellular peptide epitopes were used as Ag, the DQ2 surface levels and peptide affinity were the major regulators of T cell responses. The differential effect of DM on stimulation of the two groups of T cell clones implies differences in DQ2 presentation pathways associated with nonpathogen- and pathogen-derived Ags in vivo.
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Affiliation(s)
- Shu-Chen Hung
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305.,Program in Immunology, Stanford University, Stanford, CA 94305
| | - Tieying Hou
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305.,Program in Immunology, Stanford University, Stanford, CA 94305
| | - Wei Jiang
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305.,Program in Immunology, Stanford University, Stanford, CA 94305
| | - Nan Wang
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305.,Program in Immunology, Stanford University, Stanford, CA 94305
| | - Shuo-Wang Qiao
- Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.,K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, 0424 Oslo, Norway
| | - I-Ting Chow
- Benaroya Research Institute at Virginia Mason, Seattle, WA 98101
| | - Xiaodan Liu
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305.,Program in Immunology, Stanford University, Stanford, CA 94305
| | - Sjoerd H van der Burg
- Department of Medical Oncology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
| | - David M Koelle
- Department of Medicine, University of Washington, Seattle, WA 98195.,Department of Laboratory Medicine, University of Washington, Seattle, WA 98195; and.,Department of Global Health, University of Washington, Seattle, WA 98195
| | - William W Kwok
- Benaroya Research Institute at Virginia Mason, Seattle, WA 98101
| | - Ludvig M Sollid
- Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway.,K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, 0424 Oslo, Norway
| | - Elizabeth D Mellins
- Division of Human Gene Therapy, Department of Pediatrics, Stanford University, Stanford, CA 94305; .,Program in Immunology, Stanford University, Stanford, CA 94305
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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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9
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Yukimasa N, Sato S, Oboshi W, Watanabe T, Uzawa R. Influence of single nucleotide polymorphisms of cytokine genes on anti-HBs antibody production after hepatitis B vaccination in a Japanese young adult population. THE JOURNAL OF MEDICAL INVESTIGATION 2017; 63:256-61. [PMID: 27644568 DOI: 10.2152/jmi.63.256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Hepatitis B (HB) vaccination is one of the most efficient tools to prevent the transmission of the virus. Considerable variability exists in HB vaccine responses, with 5-10% of healthy Japanese adults demonstrating no response following a standard vaccination. Recently, polymorphisms of immune-regulatory genes, such as cytokine genes, have been reported to influence the immune response to HB vaccine. The aim of this study was to investigate the underlying mechanisms of the genetic association between several cytokine gene polymorphisms and the immune response to HB vaccination in a Japanese population. One hundred and twenty three vaccinated young adults were classified according to the level of antibody-titer (anti-HBs). Single nucleotide polymorphism typing for IFN-γ (+874, 3'-UTR), IL-10 (-591, -819, -1082), and TNF-α (-308, -857), was accomplished using the PCR-RFLP or SSP-PCR method. The TNF-α (-857) CC type and the IL-10 (-1082) AG type were present more frequently in the low titer group than in the high titer group. The TNF-α (-857) CC type was found to be significantly associated with low response of serum anti-HBs. The anti-HBs antibody was not readily produced in the IL-10 (-1082) AG and TNF-α (-857) CC haplotype. Conversely, the antibody was readily produced in the IL-10 (-1082) AA and TNF-α (-857) CC haplotype, and the IL-10 (-1082) AA and TNF-α (-857) CT haplotype, suggesting a high likelihood of the IL-10 (-1082) AG type to be included in the low anti-HBs group, and high anti-HBs antibody production in those with the TNF-α (-857) CT type. These SNPs may produce ethnically-specific differences in the immune response to HB vaccine in the Japanese population. J. Med. Invest. 63: 256-261, August, 2016.
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Affiliation(s)
- Nobuyasu Yukimasa
- Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences
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Anania C, Olivero F, Spagnolo A, Chiesa C, Pacifico L. Immune response to vaccines in children with celiac disease. World J Gastroenterol 2017; 23:3205-3213. [PMID: 28566880 PMCID: PMC5434426 DOI: 10.3748/wjg.v23.i18.3205] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/07/2017] [Accepted: 04/12/2017] [Indexed: 02/07/2023] Open
Abstract
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients.
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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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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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Chung HA, Lee SY, Moon HW, Kim JH, Sung IK, Park HS, Shim CS, Han HS. Does the antibody production ability affect the serum anti- Helicobacter pylori IgG titer? World J Gastrointest Pathophysiol 2016; 7:288-295. [PMID: 27574567 PMCID: PMC4981769 DOI: 10.4291/wjgp.v7.i3.288] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Revised: 06/05/2016] [Accepted: 07/13/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship between serum titers of anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and hepatitis B virus surface antibody (HBsAb).
METHODS: Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen (HBsAg)/HBsAb serologic assay, pepsinogen (PG) assay, and H. pylori serologic test on the same day. Subjects were excluded if they were positive for HBsAg, had a recent history of medication, or had other medical condition(s). We analyzed the effects of the following factors on serum titers of HBsAb and the anti-H. pylori IgG: Age, density of H. pylori infiltration in biopsy samples, serum concentrations of PG I and PG II, PG I/II ratio, and white blood cell count.
RESULTS: Of 111 included subjects, 74 (66.7%) exhibited a positive HBsAb finding. The serum anti-H. pylori IgG titer did not correlate with the serum HBsAb titer (P = 0.185); however, it correlated with the degree of H. pylori infiltration on gastric biopsy (P < 0.001) and serum PG II concentration (P = 0.042). According to the density of H. pylori infiltration on gastric biopsy, subjects could be subdivided into those with a marked (median: 3.95, range 0.82-4.00) (P = 0.458), moderate (median: 3.37, range 1.86-4.00), and mild H. pylori infiltrations (median: 2.39, range 0.36-4.00) (P < 0.001). Subjects with a marked H. pylori infiltration on gastric biopsy had the highest serological titer, whereas in subjects with moderate and mild H. pylori infiltrations titers were correspondingly lower (P < 0.001). After the successful eradication, significant decreases of the degree of H. pylori infiltration (P < 0.001), serum anti-H. pylori IgG titer (P < 0.001), and serum concentrations of PG I (P = 0.028) and PG II (P = 0.028) were observed.
CONCLUSION: The anti-H. pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H. pylori infection, regardless of the HBsAb titer after HBV vaccination.
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Zorzetto M, Ricevuti G, Martinetti M, Gritti D, Gasparetto C, De Silvestri A, Salvaneschi L, Cuccia M. HLA and Hypocomplementemia: The Disadvantage of Carrying the HLA-B35 and the Silent Alleles of the C4 Complement Component. Int J Immunopathol Pharmacol 2016; 17:307-16. [PMID: 15461865 DOI: 10.1177/039463200401700311] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Hypocomplementemia is an extremely complex phenomenon: we devoted our attention to its immunogenetic basis, particularly to the HLA haplotypes involved and to the study of C4 polymorphic genes. With this in mind we analyzed a group of unrelated patients with hypocomplementemia and 15 families suffering from specific C4 deficiency. Firstly, we performed a population analysis in order to identify a statistically significant association: HLA-B35 and C4BQ0 alleles, in the total group of hypocomplementemic individuals, seem to be associated with the primary disease. Secondly, we defined HLA haplotypes clear-cut segregation in the hypocomplementemic families and we identified the most common HLA haplotypes carrying B35 and C4 null allele associated with this condition. With the aid of correspondence analysis and the Transmission Disequilibrium Test (TDT), we measured the strength of this association. In this work, mainly through family analysis, we envisaged a potentially interesting genomic trait, within HLA, close to B locus, that seems to be involved in hypocomplementemia itself and perhaps in hypocomplementemia-related disorders.
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Affiliation(s)
- M Zorzetto
- Laboratorio di Biochimica e Genetica, Clinica Malattie Respiratorie, IRCCS Policlinico S.Matteo, Universitá di Pavia, Italy
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Association of HLA-DP variants with the responsiveness to Hepatitis B virus vaccination in Korean Infants. Vaccine 2016; 34:2602-7. [PMID: 27083422 DOI: 10.1016/j.vaccine.2016.03.090] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 03/15/2016] [Accepted: 03/28/2016] [Indexed: 12/13/2022]
Abstract
Recently, HLA-DP single nucleotide polymorphisms (SNPs) have been reported to be related to responsiveness to hepatitis B virus (HBV) vaccination. The aim of this study was to investigate associations between HLA-DP SNPs and responsiveness to HBV vaccine in Korean infants. A total of 290 healthy Korean infants who were registered to Seoul Metropolitan Public Cord Blood Bank during the period of February 2007 to December 2011 were enrolled. Anti-HBs antibody level was analyzed after three doses of HBV vaccination. Genotyping of HLA-DPA1 SNPs (rs3077 and rs3830066) and HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were performed by PCR-sequencing. HLA-A, -B, and -DRB1 genotyping was also performed by PCR-sequence-specific oligonucleotide probe kits. HLA-DPB1 SNPs (rs7770370, rs7770501, rs3128961, and rs9277535) were associated with HBV vaccine response. Allele frequencies of rs7770370 A, rs7770501 C, rs3128961 G, and rs9277535 A were significantly higher in responders than in non-responders (all p<0.01). Anti-HBs antibody levels were different according to genotypes of DPB1 rs7770370, rs7770501, rs3128961, and rs9277535 (all p<0.01). In multivariate analysis, HLA-DPB1 rs7770370 AA genotype was significantly associated with HBV vaccine response (relative risk, RR=2.5, p=0.033) and high-titer vaccine response (RR=2.7, p<0.001). In conclusion, HLA-DPB1 SNPs were significantly associated with responses to HBV vaccination in Korean infants.
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Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2015; 22:875-82. [PMID: 26018535 DOI: 10.1128/cvi.00148-15] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2015] [Accepted: 05/19/2015] [Indexed: 12/16/2022]
Abstract
The impaired synthesis of antigen-specific antibodies, which is indispensable for an adaptive immune response to infections, is a fundamental pathomechanism that leads to clinical manifestations in children with antibody production defects. The aim of this study was to evaluate the synthesis of antigen-specific antibodies following immunization in relation to peripheral blood B cell subsets in young children with hypogammaglobulinemia. Twenty-two children, aged from 8 to 61 months, with a deficiency in one or more major immunoglobulin classes participated in the study. Postvaccination antibodies against tetanus and diphtheria toxoids, the surface antigen of the hepatitis B virus, and the capsular Haemophilus influenzae type b polysaccharide antigen were assessed along with an immunophenotypic evaluation of peripheral blood B lymph cell maturation. A deficiency of antibodies against the tetanus toxoid was assessed in 73% of cases and that against the diphtheria toxoid was assessed in 68% of cases, whereas a deficiency of antibodies against the surface antigen of the hepatitis B virus was revealed in 59% of the children included in the study. A defective response to immunization with a conjugate vaccine with the Haemophilus influenzae type b polysaccharide antigen was demonstrated in 55% of hypogammaglobulinemic patients. Increased proportions of transitional B lymph cells and an accumulation of plasmablasts accompanied antibody deficiencies. The defective response to vaccine protein and polysaccharide antigens is a predominating disorder of humoral immunity in children with hypogammaglobulinemia and may result from a dysfunctional state of the cellular elements of the immune system.
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Wu TW, Chen CF, Lai SK, Lin HH, Chu CC, Wang LY. SNP rs7770370 in HLA-DPB1 loci as a major genetic determinant of response to booster hepatitis B vaccination: results of a genome-wide association study. J Gastroenterol Hepatol 2015; 30:891-9. [PMID: 25389088 DOI: 10.1111/jgh.12845] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/04/2014] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM Hepatitis B (HB) vaccination is highly effective in reducing the risk of hepatitis B virus infection. However, breakthrough and chronic hepatitis B virus infections in vaccinated subjects raised concern about its long-term efficacy. The specific aim of the study was to explore the host genetic determinants of long-term immunological memory against HB vaccination. METHODS We conducted a case-control study nested in a cohort of HB booster recipients who had received primary HB vaccination during infancy but failed to reside an anti-HBs titers ≥ 10 mIU/mL at the age of 15-18 years. We used a genome-wide single nucleotide polymorphism (SNP) array plate to scan autosomal chromosomes and assayed the human leukocyte antigen (HLA)-DPB1 genotype by sequence-based techniques. RESULTS We found that 10 of the 112 candidate SNPs (P-value < 5.0 × 10(-5) ) clustered within a 47-Kb region of the HLA-DP loci. All the minor alleles of these HLA-DP candidate SNPs were correlated with lower likelihoods of nonresponse to HB vaccine. There was a significant linkage disequilibrium between these HLA-DP candidate SNPs and HLA-DPB1 protective alleles. Multivariate analyses showed that rs7770370 was the most significant genetic factor. As compared with rs7770370 GG homozygotes, adjusted odds ratios were 0.524 (95% confidence interval, 0.276-0.993) and 0.095 (95% confidence interval, 0.030-0.307) for AG heterozygotes and AA homozygotes, respectively. CONCLUSION Our results showed that rs7770370 was the most significant genetic factor of response to HB booster. The rs7770370 and nearby SNPs may also contribute to the long-term immunological memory against HB vaccination.
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Affiliation(s)
- Tzu-Wei Wu
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
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18
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Newport MJ. The genetic regulation of infant immune responses to vaccination. Front Immunol 2015; 6:18. [PMID: 25699041 PMCID: PMC4313718 DOI: 10.3389/fimmu.2015.00018] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 01/09/2015] [Indexed: 12/16/2022] Open
Abstract
A number of factors are recognized to influence immune responses to vaccinations including age, gender, the dose, and quality of the antigen used, the number of doses given, the route of administration, and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, and cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b, and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.
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Affiliation(s)
- Melanie J. Newport
- Division of Clinical Medicine, Brighton and Sussex Medical School, Brighton, UK
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Komatsu H, Murakami J, Inui A, Tsunoda T, Sogo T, Fujisawa T. Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children. BMC Res Notes 2014; 7:789. [PMID: 25376093 PMCID: PMC4230755 DOI: 10.1186/1756-0500-7-789] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Accepted: 10/24/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection. METHODS This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children. RESULTS Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model. CONCLUSION Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.
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Affiliation(s)
- Haruki Komatsu
- />Department of Pediatrics, Toho University, Sakura Medical Center, 564-1 Shimoshizu Sakura, Chiba, 285-8741 Japan
- />Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Jun Murakami
- />Division of Pediatrics and Perinatology, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Ayano Inui
- />Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Tomoyuki Tsunoda
- />Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Tsuyoshi Sogo
- />Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Tomoo Fujisawa
- />Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
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Zanoni G, Contreas G, Valletta E, Gabrielli O, Mengoli C, Veneri D. Normal or defective immune response to Hepatitis B vaccine in patients with diabetes and celiac disease. Hum Vaccin Immunother 2014; 11:58-62. [PMID: 25483516 DOI: 10.4161/hv.34309] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
A defective production of protective levels of antibodies to Hepatitis B (HB) vaccine is reported to occur in 4-10% of healthy subjects and a correlation with the presence of specific human leukocyte antigen (HLA) molecules, including DQ2, which also confers genetic predisposition to celiac disease (CD) and type I diabetes mellitus (T1DM), has been suggested. The aim of this study was to analyze the serological response to HB vaccine and measles-containing vaccines in 69 diabetic patients (T1DM), 42 patients with celiac disease (CD) and 79 healthy control subjects (CT). The median interval between the third dose of HB vaccine and serum collection was 6.8, 3.5, and 4.7 years for T1DM, CD and CT groups, respectively. 50/69 (72%) T1DM patients, 32/42 (76%) CD patients and 61/79 (77%) CT subjects showed protective anti-HBs antibodies after vaccination, with no statistically significant difference. On the contrary, a lower statistically significant difference was found in the mean HBsAb level of T1DM subjects when compared with the other two groups. No correlation between HLA DQ2 expression in T1DM and vaccine response was detected. The comparison of serological response to measles after vaccination also showed no statistically significant differences in the three groups. Contrasting results between these data and those reported in the literature might be due to differences in the time intervals between vaccination and testing. Prospective studies in pathological and healthy groups with the same age at HBV vaccination and with the same time interval for blood sample collection to determine antibody titers are necessary in order to provide more conclusive data.
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Affiliation(s)
- Giovanna Zanoni
- a Department of Pathology and Diagnostics; Section of Immunology; University of Verona; Italy
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Filippelli M, Lionetti E, Gennaro A, Lanzafame A, Arrigo T, Salpietro C, La Rosa M, Leonardi S. Hepatitis B vaccine by intradermal route in non responder patients: An update. World J Gastroenterol 2014; 20:10383-10394. [PMID: 25132754 PMCID: PMC4130845 DOI: 10.3748/wjg.v20.i30.10383] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 03/12/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.
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Orson FM, Wang R, Brimijoin S, Kinsey BM, Singh RA, Ramakrishnan M, Wang HY, Kosten TR. The future potential for cocaine vaccines. Expert Opin Biol Ther 2014; 14:1271-83. [PMID: 24835496 DOI: 10.1517/14712598.2014.920319] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine's pharmacodynamic effects. AREAS COVERED This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness. EXPERT OPINION Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes.
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Affiliation(s)
- Frank M Orson
- Center for Translational Research in Inflammatory Diseases, Baylor College of Medicine, Department of Medicine , Bldg. 109, Rm. 234, 2002 Holcombe Blvd, Houston, TX 77030 , USA +1 713 794 7960 ; +1 713 794 7938 ;
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Posteraro B, Pastorino R, Di Giannantonio P, Ianuale C, Amore R, Ricciardi W, Boccia S. The link between genetic variation and variability in vaccine responses: Systematic review and meta-analyses. Vaccine 2014; 32:1661-9. [DOI: 10.1016/j.vaccine.2014.01.057] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 12/23/2013] [Accepted: 01/24/2014] [Indexed: 01/11/2023]
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HLA-DPB1 and anti-HBs titer kinetics in hepatitis B booster recipients who completed primary hepatitis B vaccination during infancy. Genes Immun 2013; 15:47-53. [DOI: 10.1038/gene.2013.62] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 10/21/2013] [Accepted: 10/24/2013] [Indexed: 12/23/2022]
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Naturally occurring hepatitis B virus B-cell and T-cell epitope mutants in hepatitis B vaccinated children. ScientificWorldJournal 2013; 2013:571875. [PMID: 24379746 PMCID: PMC3860134 DOI: 10.1155/2013/571875] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Accepted: 09/24/2013] [Indexed: 12/17/2022] Open
Abstract
To control hepatitis B virus (HBV) infection, a universal HBV vaccination program for infants was launched in Taiwan in 1984. The aim of this study was to investigate the role of B-cell and T-cell epitope variations of HBsAg and polymerase in HBV infection in vaccinated children. One hundred sixty-three sera from vaccinated children were enrolled randomly. HBV serum markers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were detected by ELISA. Nucleotide sequences encoding the S and the pre-S regions of HBsAg were analyzed in all HBsAg positive sera. Five children were HBsAg positive. Sequence analysis of S, pre-S, and overlapped polymerase (P) genes showed that HBV isolates of HBsAg-positive vaccinees were variants; no G145R but G145A and other substitutions were found in the “a” determinant. Fifteen, six, and eight amino acid substitutions within B-cell and T-cell epitopes of S, pre-S, and P regions were detected, respectively. Several immune-epitope mutants, such as S45T/A, N131T, I194V, and S207N in S, were detected in all isolates. In conclusion, our results suggested that these naturally occurring immunoepitope mutants, which changed their immunogenicity leading to escape from immune response, might cause HBV infection.
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Elrashidy H, Elbahrawy A, El-Didamony G, Mostafa M, George NM, Elwassief A, Saeid Mohamed AG, Elmestikawy A, Morsy MH, Hashim A, Abdelbasseer MA. Antibody levels against hepatitis B virus after hepatitis B vaccination in Egyptian diabetic children and adolescents. Hum Vaccin Immunother 2013; 9:2002-2006. [PMID: 23787761 PMCID: PMC3906368 DOI: 10.4161/hv.25426] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 06/03/2013] [Accepted: 06/15/2013] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The remarkable effectiveness of universal infantile hepatitis B (HB) vaccination is well documented in many countries. Nevertheless, the influence of insulin-dependent diabetes mellitus (IDDM) on the sero-protective level of antibody to hepatitis B surface antigen (anti-HBs) after HB vaccination has not been investigated in Egyptian children. The aim of this study was to investigate long-term anti-HBs sero-protective levels after infantile HB vaccination in Egyptian IDDM children. RESULTS The mean age of the healthy children was 10.86 ± 1.21 y (range, 5.5-15 y); 49 (45.8%) were boys and 58 (54.2%) were girls. The mean age of the IDDM children was 10.29 ± 3.04 y (range, 4-17 y); 32 (50.8%) were boys and 31 (49.2%) were girls. There were no significant differences between the healthy and IDDM children with respect to age and sex (p>0.05). Among the 107 healthy children, 43 (40%) did not have a protective anti-HBs level (anti-HBs<10 IU/L) and 64 (60%) had a protective level (anti-HBs ≥ 10 IU/L). In contrast, among the IDDM children, 44 (69.8%) and 19 (30.2%) did not and did have protective anti-HBs levels, respectively. This difference in anti-HBs concentration between healthy and diabetic children was highly significant (p<0.001). None of the vaccinated healthy or IDDM children was reactive to HBsAg or total anti-HBc. PATIENTS AND METHODS A total of 170 children (81 boys, 89 girls) who had been routinely vaccinated against HB were included. Their mean age was 10 ± 2.1 y. The enrolled children were divided into healthy (n = 107) and IDDM (n = 63) cohorts. Body Mass Index and levels of hepatitis B surface antigen (HBsAg), total antibody to hepatitis B core antigen (anti-HBc), and anti-HBs were evaluated in all children. In addition, the duration of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) were measured in IDDM children. CONCLUSION Our results are alarming. It appears that the majority of Egyptian diabetic children vaccinated against HB may not have sufficient anti-HBs levels to protect them from HB. Moreover, this study emphasizes the need for a population-based strategy for the management of patients without an anti-HBs protective level after HB vaccination and justifies the need to elucidate the heritability of those children.
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Affiliation(s)
- Heba Elrashidy
- Department of Microbiology and Botany; Faculty of Science; Al-Zakazik University; Al-Zakazik, Egypt
| | - Ashraf Elbahrawy
- Department of Internal Medicine; Al-Azhar School of Medicine; Al-Azhar University; Cairo, Egypt
| | - Gamal El-Didamony
- Department of Microbiology and Botany; Faculty of Science; Al-Zakazik University; Al-Zakazik, Egypt
| | - Mohamed Mostafa
- Department of Pediatrics; Al-Azhar School of Medicine; Al-Azhar University; Cairo, Egypt
| | - Nilly M George
- Department of Botany; Faculty of Science, Al-Zakazik University; Al-Zakazik, Egypt
| | - Ahmed Elwassief
- Department of Internal Medicine; Al-Azhar School of Medicine; Al-Azhar University; Cairo, Egypt
| | | | - Amr Elmestikawy
- Department of Internal Medicine; Al-Azhar School of Medicine; Al-Azhar University; Cairo, Egypt
| | - Mohamed Hanafy Morsy
- Department of Clinical Pathology; Al-Azhar School of Medicine; Al-Azhar University; Cairo, Egypt
| | - Alaa Hashim
- Department of Clinical Pathology; Al-Azhar School of Medicine; Al-Azhar University; Asyut, Egypt
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Wu TW, Chu CC, Ho TY, Chang Liao HW, Lin SK, Lin M, Lin HH, Wang LY. Responses to booster hepatitis B vaccination are significantly correlated with genotypes of human leukocyte antigen (HLA)-DPB1 in neonatally vaccinated adolescents. Hum Genet 2013; 132:1131-9. [DOI: 10.1007/s00439-013-1320-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Accepted: 05/26/2013] [Indexed: 12/18/2022]
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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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Immunogenecity of hepatitis A and B vaccination in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2013; 56:412-15. [PMID: 23841120 DOI: 10.1097/mpg.0b013e31827dd87d] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVES Aim of the study was to evaluate the response to hepatitis A and B vaccination in pediatric patients with inflammatory bowel disease (IBD). METHODS A total of 47 patients with IBD (25 ulcerative colitis, 14 Crohn's disease, and 8 indeterminate colitis) ages 3 to 17 years were compared with 50 healthy age- and sex-matched controls. Screening for hepatitis A and B serology was carried out before vaccination. Susceptible cases received 20 mg of recombinant DNA vaccine for hepatitis B (0, 1, and 6 months)and 720 milliELISA units of inactivated hepatitis A virus vaccine (HAV) (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 A total of 23 patients and 35 controls received HAV and protective anti-HAV antibodies were developed in all of the patients and controls (P =1.00). Forty-seven patients and 50 controls received hepatitis B vaccine and 70.2% of the patients versus 90% of the controls achieved seroprotection(anti-HBs titers 10 mIU/mL) 1 month after primary vaccination (95% confidence interval 0.71–0.87, P = 0.02). The overall seroprotection rates were 96% in controls and 85.1% in patients after the whole hepatitis B vaccination series (95% confidence interval 0.83–0.95, P = 0.08). No significant reduction was observed in antibody response among patients and controls during the follow-up period. CONCLUSIONS The rate of seroconversion to the hepatitis B vaccine was lower in pediatric patients with IBD than in healthy controls and hepatitis A vaccine was highly immunogenic among patients with IBD.
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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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Children unresponsive to hepatitis B virus vaccination also need celiac disease testing. J Pediatr Gastroenterol Nutr 2012; 55:e131. [PMID: 22576672 DOI: 10.1097/mpg.0b013e31825d4ac9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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Arababadi MK, Nasiri Ahmadabadi B, Kennedy D. Current information on the immunologic status of occult hepatitis B infection. Transfusion 2012; 52:1819-1826. [PMID: 22404554 DOI: 10.1111/j.1537-2995.2012.03575.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Hepatitis B is one of the most frequently occurring posttransfusion infections. Occult hepatitis B (OB) is a form of hepatitis B in which, despite the presence of hepatitis B virus (HBV) DNA in the serum and hepatocytes of a carrier, hepatitis B surface antigen is absent. In addition to the risk of transfusion of infection, OB can lead to cirrhosis, hepatic cancer, and reactivation of the viral duplication process in the carrier. The mechanisms responsible for progression of OB are yet to be clarified; however, some investigators have suggested that genetic and immunologic variables may play a significant role in the resistance of some individuals and sensitivity of other patients. This review addresses the current information regarding immunologic status of OB-infected patients.
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Affiliation(s)
- Mohammad Kazemi Arababadi
- Department of Microbiology, Hematology and Immunology, Faculty of Medicine, and Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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Wilde H. Editorial Commentary: Rabies Postexposure Vaccination: Are Antibody Responses Adequate? Clin Infect Dis 2012; 55:206-8. [DOI: 10.1093/cid/cis389] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Leonardi S, Vitaliti G, Garozzo MT, Miraglia del Giudice M, Marseglia G, La Rosa M. Hepatitis B vaccination failure in children with diabetes mellitus? The debate continues. Hum Vaccin Immunother 2012; 8:448-52. [PMID: 22370513 DOI: 10.4161/hv.19107] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The aim of our study was to evaluate the presence of specific antibodies against HBsAg in diabetic children (IDDM) previously vaccinated against hepatitis B virus. PATIENTS AND METHODS 110 diabetic children were retrospectively studied and 100 healthy controls were recruited. In all patients surface antigen, HBV core IgG, antibodies against HBV "e" antigen and quantitative HBV surface antibodies were detected. In 45 patients molecular typing of HLA alleles was performed. Metabolic control was evaluated as mean glycated hemoglobin (HbA1c) and all patients were compliant to insulin therapy. RESULTS 46 of 110 diabetic children (41.8%) and 16 of 100 healthy controls (16%) were found to have not anti-HBs antibodies (p < 0.0001). The mean antibody titer was found significantly-lower (p < 0.0001) in IDDM children than healthy controls. No correlation was found between antibody titer, age, duration of disease and HbA1c. We did not find any difference of gender, age, years of onset of the disease and metabolic control, between diabetics with anti-HBs antibodies and those without. CONCLUSIONS Our data confirm the reduced seroprotection rate for HBV vaccination in diabetics. However it remains poorly clarify the real clinical significance of this result. In our study no diabetic children showed markers of HBV infection.
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Arababadi MK, Pourfathollah AA, Jafarzadeh A, Hassanshahi G, Shamizadeh A, Ahmadabadi BN, Kennedy D. The status of humoral immunity in occult HBV infection in south-eastern Iranian patients. Clin Res Hepatol Gastroenterol 2011; 35:309-14. [PMID: 21310685 DOI: 10.1016/j.clinre.2010.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2010] [Revised: 11/29/2010] [Accepted: 12/02/2010] [Indexed: 02/04/2023]
Abstract
BACKGROUND Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite of absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. The aim of this study was to investigate components of humoral immunity during OBI as a possible measure of how patients respond to Hepatitis B viral infections. MATERIAL AND METHODS In this study, HBsAg-/anti-HBc+/HBV-DNA+ samples were assigned as OBI cases and SRID techniques were performed to measure levels of circulating antibodies (IgG, IgM and IgA) as well as C3, C4. In addition, complement system function was assessed by CH50. RESULTS Our results showed that the serum levels of IgG and C4 were significantly lower in OBI patients, while IgM and C3 were higher in patients when compared to healthy controls. Serum levels of IgA and CH50 were not significantly different between OBI patients and controls. DISCUSSION Based on these results, it could be concluded that although OBI patients produced elevated levels of IgM there may be a problem converting and progressing this response to generate enough IgG to overcome HBV infection.
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Affiliation(s)
- Mohammad Kazemi Arababadi
- Department of Microbiology, Hematology and Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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Mu SC, Wang GM, Jow GM, Chen BF. Impact of universal vaccination on intrafamilial transmission of hepatitis B virus. J Med Virol 2011; 83:783-90. [DOI: 10.1002/jmv.22055] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2010] [Indexed: 12/12/2022]
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Abstract
The clinical course of hepatitis B virus (HBV) infection varies from spontaneous recovery to chronic persistent infection leading to severe liver injury. Mounting evidence has recently highlighted the influence of host genotype in the complex interplay between viral and host factors. Studies in adults have suggested the existence of a genetic predisposition to HBV infection secondary to certain defects in the host response. These defects include opsonic deficiency, compromised antigen processing and presentation by human leucocyte antigen variations, attenuated T- and B-cell response, impaired cytokine and chemokine release, and production of receptors for several pertinent factors such as vitamin D and estrogen. By contrast, little is known about the genetic factors involved in the susceptibility to HBV transmission in early childhood. Herein, we review the literature regarding the association between host genetics and susceptibility to primary HBV infection, and we discuss the prospects of investigation in this field. A better understanding of HBV infection immunopathogenesis in the critical period of infancy may allow the development of optimal and innovative prevention and treatment.
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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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Abstract
OBJECTIVES There is a relationship between nonresponsiveness to hepatitis B virus (HBV) vaccine and certain human leukocyte antigen (HLA) genotypes. In healthy population, 4-10% vaccine recipients fail to produce protective levels of antibodies to the HBV vaccine after standard immunization depending upon age and the presence of various underlying diseases. Celiac disease (CD) is an HLA-associated immunological disease. It has been suggested that certain HLA haplotypes which are linked to CD are associated with nonresponse to HBV vaccine as well. The aim of this study is to assess the response to HBV vaccine prospectively in a group of CD and to explore the potential link between CD and HBV vaccine nonresponse by studying shared HLA haplotypes. PATIENTS AND METHODS Sixty-three previously diagnosed celiac patients who were on a strict gluten-free diet (GFD) and 54 healthy children were evaluated serologically for anti-HBs status. Celiac children who were anti-HBs negative at baseline were fully vaccinated prospectively, and reevaluated for the response to HBV vaccine. To estimate the role of HLA type in HBV vaccine response in celiac patients, a subgroup of both patients and control participants had HLA genotypes performed. RESULTS At enrollment, 27 (67.5%) children with CD and 48 (85.2%) healthy children were anti-HBs positive, and the difference between patients and controls was statistically significant (P<0.05). However, failure to respond to HBV vaccine was only 3.6% (response rate 96.4%) in prospectively vaccinated celiac patients. There was no relationship between HLA type and vaccine nonresponse in our study group. CONCLUSION The response to HBV vaccine in celiac children who were compliant to GFD is not different from a healthy population. CD may be one of the immune diseases associated with a high rate of HBV vaccine nonresponse but it might not be permanent and treatment with GFD and compliance to the treatment may ameliorate the immune response to HBV vaccine in celiac children.
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Li Y, Ni R, Song W, Shao W, Shrestha S, Ahmad S, Cunningham CK, Flynn PM, Kapogiannis BG, Wilson CM, Tang J. Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth. Hum Genet 2009; 126:685-96. [PMID: 19597844 PMCID: PMC2771141 DOI: 10.1007/s00439-009-0720-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2009] [Accepted: 07/05/2009] [Indexed: 12/18/2022]
Abstract
To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(-)) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration > or = 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab <10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab >1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV(+) youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines.
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Affiliation(s)
- Yufeng Li
- Department of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Rong Ni
- Department of Medicine, University of Alabama at Birmingham, Birmingham, USA
| | - Wei Song
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA
| | - Wenshuo Shao
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA
| | - Sadeep Shrestha
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA
| | - Sushma Ahmad
- Westat, 1650 Research Boulevard, Rockville, MD USA
| | | | - Patricia M. Flynn
- Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN USA
| | - Bill G. Kapogiannis
- Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda, MD USA
| | - Craig M. Wilson
- Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA
| | - Jianming Tang
- Department of Medicine, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294 USA
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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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Nemes E, Lefler E, Szegedi L, Kapitány A, Kovács JB, Balogh M, Szabados K, Tumpek J, Sipka S, Korponay-Szabó IR. Gluten intake interferes with the humoral immune response to recombinant hepatitis B vaccine in patients with celiac disease. Pediatrics 2008; 121:e1570-6. [PMID: 18519462 DOI: 10.1542/peds.2007-2446] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Patients with celiac disease, who often carry human leukocyte antigen-DR3;DQ2, are prone to inadequate response to hepatitis B immunization. We evaluated vaccine response in relation to disease activity and whether previous treatment with a gluten-free diet influences the achievement of protective antibody titers. PATIENTS AND METHODS We studied 128 children and adolescents with celiac disease and 113 age-matched control subjects. Twenty-two patients with celiac disease were prospectively immunized after diagnosis during dietary treatment (group 1). A total of 106 (group 2) and the control subjects received vaccination by mass immunization in schools at 14 years of age regardless of diet status and when celiac disease was still undiagnosed in 27 of these children. Diet compliance and celiac disease activity were monitored by measurement of antibodies against transglutaminase and endomysium. Vaccine response was determined by measuring antihepatitis B antibodies from serum. RESULTS The seroconversion after hepatitis B vaccination was 95.5% in group 1. All of these patients carried human leukocyte antigen DQ2. The response rate in group 2 was 50.9% and correlated with gluten intake (untreated patients: 25.9%, non-strict diet: 44.4%, strict diet: 61.4%). Treated and compliant patients did not significantly differ from control subjects (75.2%). Thirty-seven antihepatitis B-negative patients with celiac disease received a booster during a controlled gluten-free diet, and 36 (97.3%) seroconverted, irrespective of the presence of human leukocyte antigen DQ2. CONCLUSIONS Nonresponse to recombinant hepatitis B surface antigen may be a sign of undiagnosed celiac disease. However, there is a good vaccine response in adequately treated patients. Human leukocyte antigen DQ alleles do not seem to have a primary role. Revaccination is recommended during a controlled gluten-free diet.
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Affiliation(s)
- Eva Nemes
- Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, H-4032 Debrecen, Hungary.
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Lin HH, Liao HWC, Lin SK, Wang LY. HLA and response to booster hepatitis B vaccination in anti-HBs-seronegative adolescents who had received primary infantile vaccination. Vaccine 2008; 26:3414-20. [PMID: 18501999 DOI: 10.1016/j.vaccine.2008.04.038] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2008] [Revised: 03/11/2008] [Accepted: 04/15/2008] [Indexed: 12/18/2022]
Abstract
To explore contemporarily genetic and non-genetic determinants of long-term immunological memory to hepatitis B (HB) vaccination, we conducted a case-control study nested in an adolescent cohort of booster recipients who had received primary infantile HB vaccination but with residual anti-HBs titers <10 mIU/mL at 15-18 years of age. High-resolution phenotypes of human leukocyte antigen (HLA)-A, -B, and -DRB1 loci were determined by sequence-specific oligonucleotide probe hybridization. After controlling for pre-booster anti-HBs levels, the absences of HLA-A*02 and -DRB1*08, simply expressed as A*02(-) and -DRB1*08(-), and the presence of B*15 were significantly associated with elevated risks of non-response (post-booster anti-HBs titers<10 mIU/mL) to booster vaccination. The adjusted odds ratios (ORs) were 3.85 (CI, 1.82-8.33), 4.55 (CI, 1.23-16.67), 3.59 (CI, 1.40-9.17), respectively. There was multiplicative synergism between A*02 and B*15 on the risk of non-response to booster vaccination. The multivariate-adjusted ORs for A*02(-)/B*15, A*02(-)/B*15(-), A*02/B*15, and A*02/B*15(-) haplotypes were 20.39 (p=0.0003), 3.29 (p=0.007), 1.32 (p>0.05), and 1.0, respectively. Recent cigarette smoking and/or betel-quid chewing was associated with a 12-fold risk of non-response to booster vaccination. Further comparisons between responders and adolescents who had undetectable post-booster anti-HBs titers (<0.1 mIU/mL) demonstrated similar results. Our results indicated that response to booster HB vaccination as well as long-term immunological responses to HB vaccination are closely related with host genetic factors, and probably modified by recent substance use.
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Hennig BJ, Fielding K, Broxholme J, Diatta M, Mendy M, Moore C, Pollard AJ, Rayco-Solon P, Sirugo G, van der Sande MA, Waight P, Whittle HC, Zaman SM, Hill AV, Hall AJ. Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS One 2008; 3:e1898. [PMID: 18365030 PMCID: PMC2268746 DOI: 10.1371/journal.pone.0001898] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2007] [Accepted: 02/26/2008] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc. METHODS We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals. RESULTS In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of < 0.6 or > 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011). CONCLUSION This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination.
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Affiliation(s)
- Branwen J Hennig
- London School of Hygiene & Tropical Medicine, London, United Kingdom.
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Ni YH, Huang LM, Chang MH, Yen CJ, Lu CY, You SL, Kao JH, Lin YC, Chen HL, Hsu HY, Chen DS. Two decades of universal hepatitis B vaccination in taiwan: impact and implication for future strategies. Gastroenterology 2007; 132:1287-93. [PMID: 17433322 DOI: 10.1053/j.gastro.2007.02.055] [Citation(s) in RCA: 244] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2006] [Accepted: 01/11/2007] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Following the world's first successful implementation of a universal hepatitis B virus (HBV) vaccination program for infants in Taiwan 20 years ago, we performed this study to evaluate the long-term protection afforded by HBV vaccination and to rationalize further prevention strategies. METHODS HBV seromarkers, including hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) and core antigen (anti-HBc), were studied in 18,779 subjects from neonates to adults below 30 years of age in 2004. The birth cohort effect was evaluated by comparing the results of the same birth cohorts at different ages among this survey and the previous 1984, 1989, 1994, and 1999 surveys. RESULTS The seropositive rates for HBsAg, anti-HBs, and anti-HBc were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (<20 years of age) in 2004. A positive maternal HBsAg status was found in 89% of the HBsAg seropositive subjects born after the vaccination program. The absence of an increase in HBsAg seropositive subjects at different ages in the same birth cohorts born after the vaccination program implied no increased risk of persistent HBV infection with aging. CONCLUSIONS Universal HBV vaccination provides long-term protection up to 20 years, and a universal booster is not indicated for the primary HBV vaccinees before adulthood. Maternal transmission is the primary reason for vaccine failure and is the challenge that needs to be addressed in future vaccination programs. This may include an appropriate hepatitis B immunoglobulin administration strategy for high-risk infants and involve efforts to minimize noncompliance.
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Affiliation(s)
- Yen-Hsuan Ni
- Department of Pediatrics, Hospital and College of Medicine, National Taiwan University, Genomics Research Center, Taipei, Taiwan
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Park SD, Markowitz J, Pettei M, Weinstein T, Sison CP, Swiss SR, Levine J. Failure to respond to hepatitis B vaccine in children with celiac disease. J Pediatr Gastroenterol Nutr 2007; 44:431-5. [PMID: 17414139 DOI: 10.1097/mpg.0b013e3180320654] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To determine whether children with celiac disease (CD) fail to show a response to hepatitis B virus (HBV) vaccine more frequently than children without CD. PATIENTS AND METHODS This was a prospective study that compared the response to HBV, tetanus, rubella, and Haemophilus influenzae type b (Hib) vaccines between children with CD and age- and sex-matched control subjects. RESULTS The study population included 26 patients with CD and 18 age- and sex-matched controls. All had received the full complement of childhood vaccinations. A significantly higher proportion of subjects in the CD group (14 of 26) failed to respond to HBV vaccine compared with controls (2 of 18; 53.9% vs 11.1%; P < 0.05). Patients with CD were 8.33 times more likely to test negative for hepatitis B surface antigen than control subjects (95% CI, 1.5-46.5). By contrast, all of the subjects in both groups tested positive for rubella antibodies; only 1 subject in the CD group tested negative for tetanus antibody versus none in the control group (3.9% vs 0%; P = 1.0). The percentage of subjects who tested negative for Hib antibodies was similar in the 2 groups (CD, 33.3%; control, 44.4%; P = 0.53). CONCLUSIONS More than 50% of children with CD do not show a response to standard vaccination regimens for HBV. Given the large number of children with CD throughout the world, this observation suggests that there is a large HBV-susceptible population despite widespread vaccination. Current immunization strategies may need to be reassessed to protect this population and achieve the goal of universal protection.
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Affiliation(s)
- Seung-Dae Park
- Division of Pediatric Gastroenterology and Nutrition, North Shore-Long Island Jewish Health System, New Hyde Park, NY, USA.
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Singh R, Kaul R, Kaul A, Khan K. A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol 2007; 13:1770-1787. [PMID: 17465466 PMCID: PMC4149952 DOI: 10.3748/wjg.v13.i12.1770] [Citation(s) in RCA: 179] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2006] [Revised: 01/26/2006] [Accepted: 03/07/2007] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.
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Affiliation(s)
- Rashmi Singh
- Department of Biochemistry and Microbiology, Oklahoma States University-Center of Health sciences, 1111 W. 17th St. Tulsa, OK 74107, United States.
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Martinetti M, Pacati I, Cuccia M, Badulli C, Pasi A, Salvaneschi L, Minola E, De Silvestri A, Iannone AM, Maccabruni A. Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus. Int J Immunopathol Pharmacol 2006; 19:369-78. [PMID: 16831303 DOI: 10.1177/039463200601900213] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Mother-to-infant transmission of Hepatitis C Virus (HCV) represents the major cause of pediatric HCV infection today. Immunogenetic influence has been poorly investigated and mainly confined to HLA-class II serological polymorphisms. Among 290 parities, 135 from Pavia and 155 from Bergamo, of HCV-RNA-infected Italian women, 21 babies (7.24%) were HCV-RNA positive at birth and steadily positive over 20 months of life. All the 21 infected babies and 44 randomly selected uninfected ones, born to HCV-RNA+ mothers but steadily negative for HCV-RNA during a follow-up of 2 years, and their mothers were investigated for HLA-G, -C, -DRB1, -DQA1 and -DQB1 genomic polymorphisms. Among the different covariates, HLA-Cw*07, -G*010401, -DRB1*0701, -DRB1*1401 and homozygosity for HLA-G 14bp deletion can be considered as risk factors for HCV vertical transmission. On the contrary, protection was conferred by the HLA-DQB1*06, -G*0105N, -Cw*0602, DRB1*1104 and -DRB1*1302 alleles. Our initial question was: has the immunogenetic profile any role in the protection of the fetus growing in an infected milieu and, if so, is it independent from the other non-immunogenetic parameters? The answer to both questions should be yes.
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Affiliation(s)
- M Martinetti
- Immunohematology and Transfusion Center, IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy.
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Ovsyannikova IG, Dhiman N, Jacobson RM, Poland GA. Human leukocyte antigen polymorphisms: variable humoral immune responses to viral vaccines. Expert Rev Vaccines 2006; 5:33-43. [PMID: 16451106 DOI: 10.1586/14760584.5.1.33] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Antibody formation in response to antigen stimulation remains the basis for measuring an individual's response and protection for most viral vaccines. A significant proportion of the variation in individual humoral immune response to vaccination appears to be genetic. The collection of genes found on chromosome 6 forming the human leukocyte antigen system provides one of the greatest sources of genetic variation in individuals with respect to their immunological responses. Recent research has demonstrated significant associations between vaccine response and human leukocyte antigen alleles. These associations not only explain why vaccine-induced humoral immune responses vary among individuals and between populations, but these variations may also hold the key to the development of future generations of vaccines.
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Affiliation(s)
- Inna G Ovsyannikova
- Department of Internal Medicine, Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
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