Biological sex affects vaccine efficacy and protection against influenza in mice

Abstract

Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4+ T cell and CD8+ T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naïve males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression of Tlr7 was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in the Tlr7 promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion of Tlr7 reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.

Clinical trials for COVID-19 should include sex as a variable

“…In this and other planned studies in the United States, there is no mention of donor sex. For proof of principle, a study in mice revealed that transfer of serum from immune female mice was significantly better at protecting naive mice (both males and females) against influenza than was immune serum from males (15). Immunotherapies that limit characteristics of an inflammatory cascade, e.g., the IL-6 inhibitor tocilizumab, are being tested in studies that enrolled 86% males, with no indication of comparisons between the sexes (16).…”

The Use of Analgesics during Vaccination with a Live Attenuated Yersinia pestis Vaccine Alters the Resulting Immune Response in Mice

“…It is important to note that we only examined female mice in this current study. Male subjects should be examined during advanced development of novel vaccines, and there are documented differences in vaccine efficacy depending upon the sex of the vaccinee [128,129]. However, the inclusion of male mice results in confounding variables that are problematic during vaccine discovery.…”

<p>Immunoinformatics and Vaccine Development: An Overview</p>

“…148,149 There are differential antibody responses to rubella and measles viral protein between males and females and that both hormonal and genetic difference may be influencing the immune responses. 148,150,151 Practical issues may stand in the way of achieving this new development (personalized vaccinology). Having to use different vaccines for different persons based because of personal genetic composition requires more time and labor during the vaccination process.…”