Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations

Yücesoy, Berran; Talzhanov, Yerkebulan; Johnson, Victor J.; Wilson, Nevin W.; Biagini, Raymond E.; Wang, Wei; Frye, Bonnie; Weissman, David N.; Germolec, Dori R.; Luster, Michael I.; Barmada, M. Michael

doi:10.1016/j.vaccine.2013.09.026

Cited by 42 publications

(35 citation statements)

References 44 publications

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“…We found in this study that neither gender nor viremia affected the YF-17D response. We cannot rule out the impact of polymorphisms in genes involved in cytokines or HLA molecules in the vaccine response (36)(37)(38)(39). Studies with greater numbers of volunteers would be required to address their effect on the YF-17D response.…”

Section: Discussionmentioning

confidence: 99%

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

et al. 2014

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Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Conclusion.Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.Trial registration. Registration is not required for observational studies.

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Section: Discussionmentioning

confidence: 99%

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

et al. 2014

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“…Important factors that may influence vaccine efficacy in infants and children is the occurrence of genetic variability within the major histocompatibility complex (MHC) region. A number of single nucleotide polymorphisms (SNPs) within MHC class I and II genes are associated with a specific antibody response, immunoglobulin, and IgG subclasses production (23,24). Additionally, immunogenetic studies have also shown associations between polymorphisms in gene-encoding immune response proteins and variation in response to vaccines.…”

Section: Discussionmentioning

confidence: 99%

Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

Szczawińska-Popłonyk

Bręborowicz

Samara

et al. 2015

Clin Vaccine Immunol

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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. A ntibody production defects are the most common category of pediatric primary immunodeficiencies (PIDs) (1, 2). The hallmark of these immunodeficiency conditions is the defective production of antigen-specific antibodies that are an indispensable element of the adaptive immune response to pathogens (3, 4). While the poor response to vaccines is another feature of humoral PIDs, the ability to synthesize postvaccination antibodies against toxoids and polysaccharides is the most specific expression of the immune response to antigens. In the evaluation of the immune response associated with antibody production, the response to vaccination against hepatitis B is not routinely recommended because of the large proportion of adults, up to between 1% and 3% of vaccinated individuals, who do not effectively synthesize antibodies against hepatitis B virus surface antigen (HBs). In infants and children, the efficiency of recombinant vaccines against hepatitis B, assessed on the basis of postvaccination anti-HBs antibody concentration over 10 mIU/ml, is estimated at 85% to 100% (5, 6). The minimal protective level of neutralizing antibodies against diphtheria and tetanus toxoids has been estimated at 0.01 to 0.1 IU/ml, whereas to achieve long-term immunity, a concentration of specific antibodies, up to 1.0 IU/ml, may be required. The synthesis of...

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“…This result suggests the involvement of host genetic factors in the response to vaccination. Indeed, associations of SNPs in HLA class II region with response to HB vaccines have been identified in Asian and European populations . In these previous reports, the studied individuals were vaccinated with HB vaccine designed based on the HBV genotype A2.…”

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confidence: 99%

Key HLA‐DRB1‐DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine

et al. 2018

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Approximately 5‐10% of individuals who are vaccinated with a hepatitis B (HB) vaccine designed based on the hepatitis B virus (HBV) genotype C fail to acquire protective levels of antibodies. Here, host genetic factors behind low immune response to this HB vaccine were investigated by a genome‐wide association study (GWAS) and Human Leukocyte Antigen (HLA) association tests. The GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders, 351 intermediate responders, and 735 high responders. Classical HLA class II alleles were statistically imputed using the genome‐wide SNP typing data. The GWAS identified independent associations of HLA‐DRB1‐DQB1, HLA‐DPB1 and BTNL2 genes with immune response to a HB vaccine designed based on the HBV genotype C. Five HLA‐DRB1‐DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1‐DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1‐DQB1 haplotypes, and no association was identified for any of the DPB1 alleles. In contrast, no association was identified for DRB1‐DQB1 haplotypes and DPB1 alleles in a comparison between high immune responders and healthy individuals. Conclusion: The findings in this study clearly show the importance of HLA‐DR‐DQ (i.e., recognition of a vaccine related HB surface antigen (HBsAg) by specific DR‐DQ haplotypes) and BTNL2 molecules (i.e., high immune response to HB vaccine) for response to a HB vaccine designed based on the HBV genotype C. (Hepatology 2018).

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Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations

Cited by 42 publications

References 44 publications

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Impaired Antigen-Specific Immune Response to Vaccines in Children with Antibody Production Defects

Key HLA‐DRB1‐DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine

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