Genomic determinants of antibody response to a typhoid vaccine in Indian recipients.

Typhoid is endemic in India and has high global incidence. There were large outbreaks of typhoid in India between 1990 and 2018. Available typhoid vaccines induce variable levels of protective antibodies among recipients; thus, there is variability in response to the vaccine. Interindividual genomic differences is hypothesized to be a determinant of the variability in response. We studied the antibody response of ~1000 recipients of the Vi-polysaccharide typhoid vaccine from Kolkata, India, who showed considerable variability of antibody response, i.e., anti-Vi-polysaccharide antibody level 28 days postvaccination relative to prevaccination. For each vaccinee, wholegenome genotyping was performed using the Infinium Global Screening Array (Illumina). We identified 39 SNPs that mapped to 13 chromosomal regions to be associated with antibody response to the vaccine; these included SNPs on genes LRRC28 (15q26.3), RGS7 (1q43), PTPRD (9p23), CERKL (2q31.3), DGKB (7p21.2), and TCF4 (18q21.2). Many of these loci are known to be associated with various blood cell traits, autoimmune traits and responses to other vaccines; these genes are involved in immune related functions, including TLR response, JAK-STAT signalling, phagocytosis and immune homeostasis.

Genomic associations with antibody response to an oral cholera vaccine.

Oral cholera vaccine is one of the key interventions used in our fight to end the longest pandemic of our time, cholera. The immune response conferred by the currently available cholera vaccines, as measured by serum antibody levels, is variable amongst its recipients. We undertook a genome wide association study (GWAS) on antibody response to the cholera vaccine; globally, the first GWAS on cholera vaccine response. We identified three clusters of bi-allelic SNPs, in high within-cluster linkage disequilibrium that were moderately (p < 5 × 10-6) associated with antibody response to the cholera vaccine and mapped to chromosomal regions 4p14, 4p16.1 and 6q23.3. Intronic SNPs of TBC1D1 comprised the cluster on 4p14, intronic SNPs of TBC1D14 comprised that on 4p16.1 and SNPs upstream of TNFAIP3 formed the cluster on 6q23.3. SNPs within and around these clusters have been implicated in immune cell function and immunological aspects of autoimmune or infectious diseases (e.g., diseases caused by Helicobacter pylori and malarial parasite). 6q23.3 is a prominent region harbouring many loci associated with immune related diseases, including multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, as well as IL2 and INFα response to a smallpox vaccine. The gene clusters identified in this study play roles in vesicle-mediated pathway, autophagy and NF-κB signaling. No significant effect of O blood group on antibody response to the cholera vaccine was observed in this study.