Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females

Abstract

Vaccine-induced immunity declines with age, which may differ between males and females. Using human sera collected before and 21 days after receipt of the monovalent A/Cal/09 H1N1 vaccine, we evaluated cytokine and antibody responses in adult (18–45 years) and aged (65+ years) individuals. After vaccination, adult females developed greater IL-6 and antibody responses than either adult males or aged females, with female antibody responses being positively associated with concentrations of estradiol. To test whether protection against influenza virus challenge was greater in females than males, we primed and boosted adult (8–10 weeks) and aged (68–70 weeks) male and female mice with an inactivated A/Cal/09 H1N1 vaccine or no vaccine and challenged with a drift variant A/Cal/09 virus. As compared with unvaccinated mice, vaccinated adult, but not aged, mice experienced less morbidity and better pulmonary viral clearance following challenge, regardless of sex. Vaccinated adult female mice developed antibody responses that were of greater quantity and quality and more protective than vaccinated adult males. Sex differences in vaccine efficacy diminished with age in mice. To determine the role of sex steroids in vaccine-induced immune responses, adult mice were gonadectomized and hormones (estradiol in females and testosterone in males) were replaced in subsets of animals before vaccination. Vaccine-induced antibody responses were increased in females by estradiol and decreased in males by testosterone. The benefit of elevated estradiol on antibody responses and protection against influenza in females is diminished with age in both mice and humans.

Serological identification of SARS-CoV-2 infections among children visiting a hospital during the initial Seattle outbreak

“…In comparison, the aggregated results of four studies of adults reported only 2 out of 263 individuals who had neutralizing activity >1:10,000 at 2-5 weeks post symptom onset using lentiviral pseudotype assays similar to our own 10,[31][32][33] . Our sample size is too small to draw conclusions about neutralizing immunity in children versus adults, but this is an interesting area for further study, given that children develop stronger or quicker neutralizing responses to some other viruses [34][35][36][37][38] .…”

Role of IgM and IgA Antibodies to the Neutralization of SARS-CoV-2

“…The copyright holder for this preprint this version posted August 21, 2020. ; https://doi.org/10.1101/2020.08.18.20177303 doi: medRxiv preprint of sex steroids 52,53 . Whether and to what extent this contributes to gender differences seen in clinical outcomes of COVID-19 54 remains to be investigated.…”

The non-specific and sex-differential effects of vaccines

“…The Toll-like receptor 7 gene (Tlr7) is encoded on the X chromosome and is expressed at a higher level by B cells from vaccinated female mice than by B cells from vaccinated male mice, which is associated with reduced DNA methylation in the Tlr7 promoter region in female mice 41 . Data from humans and mice further show that the female bias of antibody responses to influenza vaccination is associated with circulating oestradiol levels, such that greater concentrations of oestradiol result in greater production of antibody to the vaccine antigen 42 . Taken together, both the expression of X-linked genes and increased levels of oestradiol are associated with improved vaccine-induced immunity in females.…”