Elsevier

Current Opinion in Physiology

Volume 6, December 2018, Pages 16-20
Current Opinion in Physiology

The evolution of greater humoral immunity in females than males: implications for vaccine efficacy

https://doi.org/10.1016/j.cophys.2018.03.010Get rights and content

Highlights

  • Among vertebrates, females develop higher antibody responses to diverse antigens than males.

  • Sex differences in humoral immunity are greatest after puberty and prior to reproductive senescence.

  • Sex differences in humoral immunity involve both genetic and hormonal influences.

  • Higher B cell activity in females might improve vaccine efficacy in females compared with males.

  • Transmission of antibodies against specific microbes from mother to young protects offspring early in life.

Males and females differ in their effector and memory immune responses to foreign and self-antigens. The difference in antibody responses (i.e., humoral immunity), in particular, is one of the most well conserved sex differences in immunology. Certain sex differences in humoral immunity are present throughout life, whereas others are only apparent after puberty and prior to reproductive senescence, suggesting that both genes and hormones are involved. Importantly, these sex-based differences in humoral immunity contribute to variation in the responses to vaccines and may explain some disparities in vaccine efficacy between the sexes. Elevated humoral immunity in females compared with males is phylogenetically well conserved, suggesting an adaptive advantage of elevated antibody for reproductive success, including for the transfer of protective antibodies to offspring.

Section snippets

Ontogeny of sex differences in humoral immunity

The effects of age on the humoral immune response to vaccination are well documented, yet very few studies consider both age and sex as biological variables. Sex differences are most profound in individuals after sexual maturation, and the underlying mechanisms for these differences have been attributed to both hormonal and genetic effects on the immune system. However, the interplay between age, specifically prior to sexual maturation and following reproductive senescence, and the differential

Functional significance of sex differences in humoral immunity for vaccines

Increased susceptibility to infections in infants has led to the development of many vaccines that provide protection prior to exposure. Sex differences have been reported in the antibody responses to many childhood vaccines, however these data are conflicting and limited by the number of studies that report the sex of the individuals and/or partition their data by sex. Antibody responses to diphtheria, pertussis, hepatitis A, hepatitis B, pneumococcal, rabies, human papilloma virus (HPV), and

Phylogeny of sex differences in humoral immunity

Sex differences in humoral immune responses have evolved in diverse species. In birds, for example, females exhibit higher antibody and cell-mediated immune responses to immune challenges and these effects are often most pronounced during the mating season when male testosterone concentrations are highest [52, 53]. Mounting adaptive immune responses that are necessary for clearance of microbes requires metabolic resources that might otherwise be used for other biological processes, such as

Concluding remarks

Males and females are biologically different, which impacts adaptive immune responses to diverse antigens, including vaccine antigens. The mechanisms mediating these differences, both hormonal and genetic factors, can alter humoral immune responses to vaccination and may result in sex-specific difference in vaccine efficacy across the life course. Consideration of sex differences in the design of vaccines, including those that protect against influenza, may increase vaccine efficacy. The

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The writing of this review was supported by the NIH/NIAID Center of Excellence in Influenza Research and Surveillance contract HHS N272201400007C.

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