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.

疫苗诱导的免疫力随着年龄的增长而下降，男性和女性之间可能有所不同。使用在接受单价A / Cal / 09 H1N1疫苗之前和之后21天收集的人类血清，我们评估了成人（18-45岁）和年龄（65岁以上）个体的细胞因子和抗体反应。接种疫苗后，成年女性比成年男性或老年女性发展出更高的IL-6和抗体反应，而女性抗体反应与雌二醇浓度呈正相关。为了测试雌性小鼠对流感病毒攻击的防护是否比雄性更大，我们使用灭活的A / Cal / 09 H1N1疫苗初免和加强了成年（8-10周）和成年（68-70周）雄性和雌性小鼠的免疫力疫苗并用A / Cal / 09变异病毒进行攻击。与未接种疫苗的小鼠相比，未接种疫苗的成年小鼠但未衰老，挑战后，无论性别如何，小鼠的发病率都较低，肺病毒清除率更高。接种疫苗的成年雌性小鼠产生的抗体应答比接种疫苗的成年雄性小鼠具有更大的数量和质量，并且更具保护性。随着小鼠年龄的增长，疫苗效力的性别差异减小。为了确定性类固醇在疫苗诱导的免疫反应中的作用，对成年小鼠进行了性腺切除术，并在接种疫苗之前先将了部分动物体内的激素（雌性雌二醇和雄性睾丸激素）替代了。雌二醇增加了疫苗诱导的抗体反应，雄激素则降低了疫苗诱导的抗体反应。随着年龄的增长，雌二醇对雌性抗体应答和预防流感的益处随着小鼠和人类的年龄而降低。