Estradiol enhances influenza vaccine responses through B cell metabolic reprogramming in female mice

Vaccine-induced immunity differs between the sexes, with adult females mounting stronger antibody responses to influenza vaccination than age-matched males. We show that estradiol in females regulates B cell metabolism to promote the maturation and metabolic activation of antibody-secreting B cells, thereby enhancing humoral immunity and protection following vaccination. mTOR signaling in B cells was greater in adult females than males after vaccination, which was diminished with aging or depletion of estradiol. Therapeutic treatment of aged females with either estradiol or a selective estrogen receptor α modulator increased mTOR signaling and improved vaccine-induced antibody responses, thereby eliminating the effects of aging on influenza immunity. Harnessing estrogen-signaling mechanisms to improve responses to influenza vaccines could be a novel therapeutic strategy to improve public health.