Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

Abstract

Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed [2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid.

Genomic correlates of variability in immune response to an oral cholera vaccine

“…Individuals (n ¼ 1000), unrelated at least to the first-cousin level based on family history report, aged 14 years or older, inhabiting a socio-economically depressed locality of Kolkata (formerly, Calcutta), India, were recruited using a statistical sampling design, 34 with institutional ethical approval and written individual informed consent. Exclusions included: (a) pregnant and lactating women and (b) based on self-report, individuals who had ever been diagnosed with cholera or had suffered from diarrhea or vomiting during the week preceding recruitment.…”

“…33 Insights into the impact of genetic variation in vaccinees on AR has been obtained for some vaccines. 24,34,35 In this study, we have investigated, for the first time, whether variation in the genomic backgrounds of vaccinees contributed to variation in immunological response to the killed whole-cell bivalent oral cholera vaccine, which has been introduced in India in 2010.…”

Vi antigen of Salmonella enetrica serovar Typhi — biosynthesis, regulation and its use as vaccine candidate

“…This variation in immune response is due to differences at the genetic level along with environmental factors. Studies regarding genetic factors responsible for the immunological response to a vaccine may be helpful to develop a vaccine that can overcome immunogenetic restrictions [8]. Studies in endemic areas have reported that around 19-58% of patients are often exposed to S. Typhi and other related infections and therefore develop protective levels of anti-Vi antibodies in the serum prior to vaccination [22,83,84].…”

“…Studies in endemic areas have reported that around 19-58% of patients are often exposed to S. Typhi and other related infections and therefore develop protective levels of anti-Vi antibodies in the serum prior to vaccination [22,83,84]. Such observation suggest that the vaccines can induce a strong post vaccination antibody levels in individuals with/without pre-vaccination antibody levels against S. Typhi [8].…”

“…People residing in slump areas and under unhygienic conditions are more prone to infection and thus in more need of vaccination [8].…”