Conference 2022 Live Talk
Sex hormones more than sex chromosomal complement predict sex differences in influenza vaccine-induced immunity and protection in mice
Authors and Affiliations
Kumba Seddu1, Santosh Dhakal1, Abhinaya Ganesan,1 Henning Jacobsen1, Sabra L. Klein1
1. The Johns Hopkins Bloomberg School of Public Health W. Harry Feinstone Department of Molecular Microbiology and Immunology Baltimore, MD, USA
Following influenza vaccination, adult female mice have greater quantity and quality of antiviral antibodies than males, which significantly improves protection against live influenza virus challenge. Whether sex steroid hormone concentrations, sex chromosome complement, or both underlie greater immunity and protection following vaccination has not been determined. To dissect the relative contribution of sex steroid hormones and sex chromosome complement on influenza vaccine-induced immunity and protection, we used the Four Core Genotype (FCG) mouse model on a C57BL/6 background to evaluate how gonadal sex (i.e., testes or ovaries) and sex chromosome complement (i.e., XX or XY) can independently or together contribute to sex differences in immunity to influenza.
Adult (8-10 week old) FCG mice (n=20/genotype) were vaccinated intramuscularly with inactivated mouse-adapted A/California/04/09 (ma2009 H1N1) and boosted 21 days after the first dose. Blood samples were collected at several time points after vaccination to measure circulating and functional antibody responses. All mice were challenged intranasally with live mouse-adapted A/California/04/09 drift variant virus and used to either measure virus replication kinetics in the lungs or development of clinical disease.
Following vaccination, gonadal females (i.e., XXF and XYF), regardless of sex chromosome complement, produced greater antibody responses than gonadal males (i.e., XYM and XXM). After live virus challenge of vaccinated FCG mice, gonadal females had less pulmonary virus replication than gonadal males. Gonadal sex and sex chromosomal complement intersected to impact disease severity following live virus challenge, in which among gonadal females, XX females experienced less morbidity than XY females. In contrast, there was no effect of sex chromosome complement among gonadal males.
Sex steroid hormones more than sex chromosome complement underlie sex differences in influenza vaccine-induced immunity and protection. How hormones alter the activity of antibody-secreting B cells to differentially regulate responses to vaccination requires further investigation.