Sex Differences In Immune Responses To Vaccines

Sex differences in susceptibility to infections, and their clinical course and outcome, have been well described in the literature. Thus adult females generally mount more pronounced pro-inflammatory innate and adaptive immune responses to viral and bacterial infections than males, and generally males have poorer outcomes in bacterial septic shock. Despite this, few studies consider the effect of sex when analysing responses to vaccines. Females have been shown to mount stronger humoral responses to vaccines compared to males and have higher rates of adverse reactions. Additionally, adult females have been shown to up-regulate more innate immune response genes following yellow fever vaccination than males. The paucity of literature, particularly in regards to infant immunity, prompted us to examine the influence of sex on vaccine responses in more detail. We conducted a series of immunological vaccine studies in infants living in The Gambia, West Africa. We analysed for sex differences in the immunological profiles following administration of measles vaccine (MV) or diphtheria, tetanus, whole cells pertussis combined vaccine (DTwP) to nine month old infants. Assays included whole human transcriptional profile analysis, vaccine antibodies, in vitro cytokine release in response to innate stimuli or cognate antigens, as well as intracellular cytokine staining to enumerate polyfunctional T cells. There were clear sex differences in post-vaccine immunity for most of the parameters tested. Generally, male infants had more pro-inflammatory innate and adaptive immune response profiles compared to females of the same age. The sexes differed in their transcriptional profiles following vaccination, with distinct sets of genes being differentially expressed. By contrast, vaccine induced antibody responses to MV and DTwP were equivalent in male and female infants. The observation of sex differences in the immune responses elicited by vaccines has a number of important implications. It suggests that sex should be taken into account in vaccine studies; particularly for novel vaccines and in vaccine safety trials. Failing to do so may miss important data. The mechanisms are not yet known, but differences in sex hormone levels and expression of X-linked immune responses and microRNAs genes may be involved.