Abstract
A number of factors are recognized to influence immune responses to vaccinations including age, gender, the dose, and quality of the antigen used, the number of doses given, the route of administration, and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, and cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b, and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.
Highlights
Infant and under-5 mortality rates are reducing, 6.6 million children died in 2012 [1]
Whilst vaccines are available for many infections and increasingly administered in developing countries, there remains an urgent need to develop or improve vaccines for this age group. The reasons for this are multiple: there are no vaccines yet for some important infections such as malaria and respiratory syncytial virus; vaccines for other diseases need improving or replacing (e.g., BCG); global differences in microbial epidemiology may render effective vaccines developed in one region ineffective in another [e.g., the human papillomavirus [2]]; vaccines that do not cover all strains of a pathogen may drive changes in the microbiological epidemiology that may render the vaccine ineffective
Not part of Expanded Program on Immunization schedules for children, genome-wide association studies (GWAS) have been conducted to detect associations with immune responses to smallpox vaccination, where significant associations were identified within a number of cytokine gene variants [44, 45], and anthrax vaccination where suggestive rather than significant associations was found with single-nucleotide polymorphisms (SNPs) located with the HLA class II loci, the mex-3 homolog C (MEX3C) gene and the splA/ryanodine receptor domain and suppressor of cytokine signaling (SOCS) box containing 1 (SPSB1) gene [46]
Summary
A number of factors are recognized to influence immune responses to vaccinations including age, gender, the dose, and quality of the antigen used, the number of doses given, the route of administration, and the nutritional status of the recipient. Several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required
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