Multigenic Control of Measles Vaccine Immunity Mediated by Polymorphisms in Measles Receptor, Innate Pathway, and Cytokine Genes

Tuesday, 21st of January 2014

[source]Vaccine[|source]

Given the multifactorial nature of diseases and the complexity of biological responses, it is highly likely that multigenic interactions affect vaccine response and immune outcomes, a process that is better explained by the immune response network theory than by a dominant allele mechanism. Taking  advantage of the wealth of existing genetic and immunologic data on healthy young recipients of two doses of MMR-II, the authors examined potential multigenic interactions associated with robust or ineffective vaccine responses.

In their report, the authors document that many biological responses, including immunity to a pathogen or vaccine, consist of a series of tightly controlled, sequentially activated, and inter-linked response pathways – in the context of pathogen exposure or vaccination.  More details and implications for novel measles vaccine development are available at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288471/

Abstract

Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. We have previously investigated the influence of genetic polymorphisms on vaccine immune response, including measles vaccines, and have shown that polymorphisms in HLA, cytokine, cytokine receptor, and innate immune response genes are associated with variation in vaccine response but do not account for all of the inter-individual variance seen in vaccinated populations. In the current study we report the findings of a multigenic analysis of measles vaccine immunity, indicating a role for the measles virus receptor CD46, innate pattern-recognition receptors (DDX58, TLR2, 4, 5,7 and 8) and intracellular signaling intermediates (MAP3K7, NFKBIA), and key antiviral molecules (VISA, OAS2, MX1, PKR) as well as cytokines (IFNA1, IL4, IL6, IL8, IL12B) and cytokine receptor genes (IL2RB, IL6R, IL8RA) in the genetic control of both humoral and cellular immune responses. This multivariate approach provided additional insights into the genetic control of measles vaccine responses over and above the information gained by our previous univariate SNP association analyses.