Genetic variation in the response to vaccination.

Vaccines are the most powerful means to prevent and diminish the burden of infectious disease. However, there are limitations to their use: vaccines are not yet available for all infectious diseases (including human immunodeficiency virus and respiratory syncytial virus), they sometimes lack efficacy, the response to vaccination is limited by maternal antibodies in very young infants, and the response to vaccination is variable or may even be absent in some individuals. This review focuses on genetic factors that determine the variable response to vaccination. The highly polymorphic human leukocyte antigen system, which is involved in antigen presentation, has been researched most in this aspect, and clearly affects the response to vaccination. Other, but less polymorphic pathways involved are the Toll-like receptor pathway, which is involved in antigen recognition and stimulation of the immune system, and the cytokine immunoregulatory network. The heritability, or the proportion of total variance that is due to additive genetic factors, appears to be particularly large for vaccine-induced antibody responses in young infants compared with cell-mediated responses and antibody responses in older, immunologically more mature individuals. Both antibody and cell-mediated responses are not only affected by loci within, but also strongly by loci outside the human leukocyte antigen system. Because most genes that are important in influencing immune responses to vaccination are still unknown, clearly more work is required. A better understanding of the factors that determine an effective response to vaccination may lead to the identification of specific genes and pathways as targets for the development of novel more uniformly effective vaccines.