Testosterone-regulated genes may affect vaccine-induced immunity

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Testosterone-regulated genes may affect vaccine-induced immunity NIH-funded study helps explain differences in male and female responses to vaccines WHAT: A new study has identified a link between certain genes affected by testosterone and antibody responses to an influenza vaccine. The findings, published in Proceedings of the National Academy of Sciences, suggest that testosterone levels may partially explain why men often have weaker responses to vaccines than women. The study, led by researchers at Stanford University, was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health.

Previous research has shown that men typically experience more severe viral and other microbial infections than women, who tend to mount stronger immune responses to infections and vaccinations. In the new study, researchers analyzed the antibody responses of 53 women and 34 men of various ages to the 2008-2009 seasonal influenza vaccine. Compared to the men, the women produced antibodies that in laboratory tests could more effectively neutralize the influenza virus.

To explain this difference, the scientists searched for patterns in gene expression, or the degree to which specific genes are turned on or off. They found that men with weak vaccine responses tended to have high expression levels of a certain cluster of genes involved in the metabolism of lipids (fats). Previous studies have suggested that testosterone may regulate the expression of many of these genes. The researchers found that men with high levels of testosterone and elevated expression of the gene cluster had weaker antibody responses to the vaccine than women and men with low testosterone. These results suggest that testosterone may suppress immune responses to vaccines by altering expression patterns of specific genes, but further research is needed to determine the mechanism.

### ARTICLE: D Furman et al. A systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1321060111 (2013).

WHO: Lynda Chiodetti, Ph.D., Chief of the Innate Immunity Section in NIAID's Division of Allergy, Immunology and Transplantation, is available to discuss the findings.

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