Associations between genetic variation and antibody responses to the measles vaccine in South African children
Date
2022
Authors
Kapelus, Daniel Justin
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Abstract
This study aimed to investigate the associations between genetic variation of a selection of candidate SNPs and the IgG antibody responses to the measles vaccine MeasBio (Biovac) in a
cohort of Black South African children (n=125). Of the 125 children, 17 were classified as seronegative (IgG titre <330 mIU/mL) and 108 were classified as seropositive (IgG titre ≥330
mIU/mL) using measles IgG antibody data gathered at 18 months of age, six months after completing the two-dose schedule of the MeasBio vaccine. Demographic variables such as sex,
birthweight, and weight at 18 months were found to not be significantly associated with serostatus.
We formulated a candidate SNP panel from the literature comprised of 77 SNPs related to innate immune responses and vaccine responses. DNA was extracted from buccal swabs
gathered from the children in a previous study, and MassARRAY technology was used to genotype the samples. PLINK (version 1.07) was used to conduct univariate and haplotype
analyses, and Microsoft Excel (version 2112) was used to analyse demographic variables.
We generated novel MAF and haplotype data for the Black South African population and found six SNPs with significant associations to measles antibody levels through allele and genotype models (P<0.05): rs10774671 (OAS1), rs1801275 (IL-4RA), rs1805015 (IL-4RA), rs2243248 (IL-4), rs2546893 (IL-12B), rs2834160 (IFNAR2). Odds ratios showed that the rs1805015, rs2546893, and rs2834160 SNPs were associated with lower measles IgG levels (seronegativity) post vaccination, while rs10774671, rs1801275, and rs2243248 SNPs were associated with higher measles IgG levels (protective against seronegativity). Three haplotypes on chromosomes 5, 16, and 20 were significantly associated with measles serostatus post vaccination. While the IFNAR2 and OAS1 SNPs relate to the interferon type I pathway, the SNPs in IL-4, IL-4RA, and IL-12B relate to the interferon type II (IFN-II) pathway, suggesting that genetic variation in interferon production plays a critical role in measles vaccine immunity. Within the IFN-II pathway, SNPs with significant associations were found in both the IL-12 and IL-4 pathways which stimulate CD4 T helper type 1 (Th1) vs CD4 T helper type 2 (Th2) immunity respectively. We did not detect significant associations between measles vaccine immunity and candidate SNPs in toll-like receptors (TLRs), cytoplasmic sensors, or the vitamin D pathway. This study is an initial study and forms a basis for future investigations into measles vaccine responses within the Black South African population
Description
A research report submitted in fulfilment of the requirements for the degree of Master of Science in Medicine (Vaccinology) to the Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, 2022