MULTIGENIC CONTROL OF MEASLES VACCINE IMMUNITY MEDIATED BY POLYMORPHISMS IN MEASLES RECEPTOR, INNATE PATHWAY, AND CYTOKINE GENES

Monday, 14th of April 2014

[source]Vaccine[|source]

Measles infection and vaccine response are complex biological processes that involve both viral and host genetic factors. Given the multi-factorial 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.

In this report, the authors take advantage of a wealth of existing genetic and immunologic data on healthy young recipients of two doses of MMR-II to examine potential multigenic interactions associated with robust or ineffective vaccine responses. The report leaves you with the optimism of understanding how immunity is controlled and likely spillovers into establishment of foundations for improving existing vaccines, identifying risk factors for adverse events, and developing effective next-generation vaccines. More details are accessible 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.