Sex differences in vaccine-induced humoral immunity

Abstract

Vaccines are among the most impactful public health interventions, preventing millions of new infections and deaths annually worldwide. However, emerging data suggest that vaccines may not protect all populations equally. Specifically, studies analyzing variation in vaccine-induced immunity have pointed to the critical impact of genetics, the environment, nutrition, the microbiome, and sex in influencing vaccine responsiveness. The significant contribution of sex to modulating vaccine-induced immunity has gained attention over the last years. Specifically, females typically develop higher antibody responses and experience more adverse events following vaccination than males. This enhanced immune reactogenicity among females is thought to render females more resistant to infectious diseases, but conversely also contribute to higher incidence of autoimmunity among women. Dissection of mechanisms which underlie sex differences in vaccine-induced immunity has implicated hormonal, genetic, and microbiota differences across males and females. This review will highlight the importance of sex-dependent differences in vaccine-induced immunity and specifically will address the role of sex as a modulator of humoral immunity, key to long-term pathogen-specific protection.

Keywords: Gender differences; Hormones; Immune response; Infection; Sex differences; Vaccination.

Fig. 1

Factors that influence sex-specific humoral immunity to vaccination. Immune response in males and females differ. Females generate higher overall antibody levels, more adverse events, have higher B cell frequencies, exhibit elevated innate immune cell phagocytic activity, etc. (pink box). Males possess increased NK cell numbers, enhanced type-1 immune responses, etc. (blue box). Genetic chromosomal differences, hormone levels, miRNA expression, sex hormones, and gender-specific differences in the microbiome are among some of the factors that underlie differential humoral immunity following vaccination (gray box on the left). However, how these parameters all interact to shape immunity and how they may be harnessed in next generation is incompletely understood