Testosterone May Affect Efficacy of Influenza Vaccine

Testosterone may play a role in the effectiveness of the influenza vaccine, according to the results of a new study. Previous studies have reported differences in immune response to infections and vaccination between men and women, with women often having stronger reactions. “There’s quite a lot of fundamental research showing weaker immune activation of cells and in model systems,” explained lead researcher David Furman, PhD, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA. It is not understood, however, exactly why there are differences in immune systems between the sexes. Furman mentioned a 2010 Lancet Infectious Diseases study demonstrating that most of the genes that change upon vaccination with the yellow fever vaccine YF-17D were only activated in women, “but the effect of these differences in the standard end point of an antibody response remained to be determined,” he said. In the current study, Furman noted that they were able to make the link between the expression of genes and the production of neutralizing antibodies. “Most importantly, we demonstrate that among men there’s quite a lot of variability, with some having a very potent antibody production and others almost negligible, and these differences could be attributed to the levels of testosterone and expression of such genes signatures,” he said. “Therefore, we link biological information with a clinical end point and show the existence of subgroups of males (having differential production of influenza-specific antibodies) based on their testosterone levels and expression of a certain cluster of genes.” Furman and colleagues analyzed the blood of 53 women and 34 men of different ages after they received the influenza vaccine. Researchers discovered a generally stronger antibody response to the vaccine and expression of inflammatory cytokines in women compared with men. This corresponded with the phosphorylated STAT3 protein levels in monocytes, but not with the serological response to the influenza vaccine. They identified a cluster of genes involved in lipid metabolism that correlated with poor virus-neutralizing activity in the male participants. Men with high testosterone levels and the gene cluster exhibited the lowest antibody responses to the influenza vaccine. Vaccine responsiveness was similar between the male participants with relatively low levels of testosterone and the female participants. While the findings in regard to the male participants having a weaker response were not surprising due to previous research, “the fact that the genes associated with these differences were shown as being modulated by testosterone in previous studies was something unexpected,” said Furman. “This set of genes seem to act together to regulate fatty acid synthesis and the link between fatty acids and the antibody response is also pretty novel.” According to Furman, the limitations of the study are related to its sample size and the mechanisms behind the genes identified by the authors and the production of antibodies, both of which are being addressed in other human and mice studies that are being conducted by the researchers. When questioned about his recommendations in terms of future research on this topic, he stated, “The most important recommendation to the scientific community is to take into consideration the sex of the specimen whether you are working with model systems or human samples, to partition the data by sex and estimate the effect of it. This is not even reported in most studies, and we know it is a source of huge biological variation.” The take-home message for vaccinologists and endocrinologists would be that “sex steroids have a huge effect in immunity and they should be aware of this when considering vaccination regimes,” said Furman. The study was published in the Proceedings of the National Academy of Sciences. -Meredith Edwards White Reference Furman D, Hejblum BP, Simon N, et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2013 Dec 23. [Epub ahead of print]