New genetic associations detected in a host response study to hepatitis B vaccine

Dávila, Sonia; Froeling, Fieke E. M.; Tan, Adrian; Bonnard, Carine; Boland, Greet J.; Snippe, H.; Hibberd, Martin L.; Seielstad, Mark

doi:10.1038/gene.2010.1

Cited by 74 publications

(54 citation statements)

References 41 publications

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“…Additionally, immunogenetic studies have also shown associations between polymorphisms in gene-encoding immune response proteins and variation in response to vaccines. Among others, associations between an SNP in the forkhead box protein 1 (FOXP1) gene, a transcription factor regulating B cell development (25) and in various cytokine genes, such as gamma interferon (IFN-␥), IL-4, IL-4R, IL-10, IL-10RA, IL-12B, and tumor necrosis factor (TNF), and the vaccine efficacy have also been shown (26,27). Another proposed inhibitory mechanism that may contribute to inadequate infant response to vaccine is related to high titers of maternal antibodies that persist over a period of 6 to 12 months.…”

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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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 6p21-22 region, harboring human major histocompatibility complex (MHC), also showed an overrepresentation of African ancestry in this study (although <3 SD) and has been reported under selection in various studies (Garrigan and Hedrick 2003;Tang et al 2007). MUC1, located in 1q22, is involved in signaling by PDGF and serves a protective function by binding to pathogens (Davila et al 2010;Li et al 2010). HBB and HBD, located in 11p15, have been subjected to balancing selections because their mutations protected against malaria according to numerous studies (Ashley-Koch et al 2000;Wood et al 2005).…”

Section: Natural Selection In African Americansmentioning

confidence: 99%

Genome-wide detection of natural selection in African Americans pre- and post-admixture

Jin¹,

Xu²,

Wang³

et al. 2011

Genome Res.

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It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre-and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific highrisk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre-and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

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“…ITGAL forms a subunit of lymphocyte function-associated antigen-1 (LFA1), together with ITGB2, and plays a central role in immune cell interaction by binding to ICAMs and regulating leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. The largest study in this field to date is that by Davila et al (Davila et al, 2010), and comprised a two-stage screen of just under 6000 SNPs in over 900 immune genes with regard to HBV vaccine failure following a two-dose immunisation schedule in 981 Indonesians. Non-response was shown to be associated with SNPs in BTNL2, IL6ST, KLRF1, LY6H, MBL2, TGFB3, HLAB, HLA-DRA, HLA-DRQB1, FOXP1, LILRB4, TGFB2, TNFSF15, C5, CCL15, with the most convincing evidence for MHC genes and the latter six genes listed.…”

Section: Genetics Of Immunity Induced By Hbv Vaccinationmentioning

confidence: 99%

Host genetic factors in hepatitis B infection, liver cancer and vaccination response: A review with a focus on Africa

Hennig

Hall

2012

Science of The Total Environment

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The disease burden due to hepatitis B virus (HBV) infection remains significant; 350 million people are infected world-wide, and around half a million deaths each year are due to HBVrelated liver disease and hepatocellular carcinoma (HCC). Infant immunisation against infection was introduced in the early 1980s, the vaccine is routinely administered across regions where the disease is endemic and has been shown to be safe and effective. However, the large number of older individuals with persistent infection means that disease will not be reduced significantly for several decades. Furthermore, failure to respond to the vaccination has been observed in about 5% of vaccinees and to date we have limited information on the durability of vaccine protection against infection. Hepatitis B infection and disease pathogenesis are known to be influenced by a number of factors including host genetics factors. This review aims to give an overview of the role of genetic variation in persistent HBV infection and the development of liver disease including HCC. Vaccine-induced immunity is, at least in part, heritable and we also discuss findings on the genetic control of responses to HBV vaccination. The epidemiology of HBV infection differs by world region, as does the genetic makeup of individuals originating from different regions. This review focuses on the situation in Africa, where hepatitis B is highly endemic.

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New genetic associations detected in a host response study to hepatitis B vaccine

Cited by 74 publications

References 41 publications

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

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

Genome-wide detection of natural selection in African Americans pre- and post-admixture

Host genetic factors in hepatitis B infection, liver cancer and vaccination response: A review with a focus on Africa

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