TY - JOUR
T1 - Multigenic control of measles vaccine immunity mediated by polymorphisms in measles receptor, innate pathway, and cytokine genes
AU - Kennedy, Richard B.
AU - Ovsyannikova, Inna G.
AU - Haralambieva, Iana H.
AU - O'Byrne, Megan M.
AU - Jacobson, Robert M.
AU - Pankratz, V. Shane
AU - Poland, Gregory A.
N1 - Funding Information:
We would like to thank the subjects who participated in our studies, and acknowledge the efforts of the research fellows and nurses working with the Mayo Vaccine Research Group. Funding support was provided by NIH grants AI33144 , AI48793 (which recently received an NIH MERIT award), and 5UL1RR024150-03 for the National Center for Research Resources (NCRR) . NCRR is a component of the National Institutes of Health and the NIH Roadmap for Medical Research. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources, the National Institute Of Allergy And Infectious Diseases or the National Institutes of Health.
PY - 2012/3/9
Y1 - 2012/3/9
N2 - 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.
AB - 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.
KW - Cytokines
KW - Immunogenetics
KW - Interferon response
KW - Measles vaccine
KW - Multigenic SNP association
KW - Toll-like receptors
KW - Vaccine response
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U2 - 10.1016/j.vaccine.2012.01.025
DO - 10.1016/j.vaccine.2012.01.025
M3 - Article
C2 - 22265947
AN - SCOPUS:84857366620
SN - 0264-410X
VL - 30
SP - 2159
EP - 2167
JO - Vaccine
JF - Vaccine
IS - 12
ER -