Estradiol replacement improves vaccine-induced antibody responses and protection against influenza in aged female mice

Abstract

Abstract Adult female mice generate greater vaccine-induced immunity and protection than their male counterparts, but this female advantage is lost with age. We hypothesized that treatment of aged female mice with exogenous estradiol would improve vaccine-induced antibody responses and protection from both pulmonary infection and disease after live influenza virus challenge. To investigate this, adult (2–3 months old) and aged (17–18 months old) female C57BL/6 mice were implanted with either empty (placebo) capsules or capsules loaded with 17β-estradiol (E2) hormone, and then vaccinated with mouse-adapted A/California/04/09 (ma2009 H1N1) vaccine. Total IgG and neutralizing antibody titers (nAb) were quantified using blood samples collected post vaccination. >1 month post vaccination, mice were challenged intranasally with ma2009 H1N1 drift variant virus. A subset of mice was euthanized at 3 days post challenge to collect lungs and measure infectious virus titer. Another subset was followed for 14 days to measure changes in body mass as a measure of disease severity. We found that aged female mice treated with E2 produced significantly greater IgG and nAb responses compared to placebo-treated aged females, and the responses of E2-treated aged females were comparable to the antibody responses generated in adult females. Treatment with E2 also reduced morbidity, but not pulmonary virus titers, following live virus challenge. Our data suggest that estrogen replacement in aged female mice improves their humoral immune response to influenza vaccination and protects them from severe disease. Supported by U54AG062333