Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females
Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females
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DOI：
10.1038/s41541-019-0124-6
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发表时间：
2019-07-12
期刊：
影响因子：
9.2
通讯作者：
Klein, Sabra L.
中科院分区：
文献类型：
--
作者：
Potluri, Tanvi;Fink, Ashley L.;Klein, Sabra L.
疫苗诱导的免疫力随着年龄的增长而下降，这可能在男性和女性之间有所不同。使用在接受单价A/Cal/09 H1N1疫苗之前和之后21天收集的人血清，我们评估了成人（18-45岁）和老年（65岁以上）个体的细胞因子和抗体应答。接种疫苗后，成年女性比成年男性或老年女性产生更大的IL-6和抗体应答，女性抗体应答与雌二醇浓度呈正相关。为了测试雌性对流感病毒攻击的保护是否大于雄性，我们用灭活A/Cal/09 H1N1疫苗或无疫苗引发和加强成年（8-10周）和老龄（68-70周）雄性和雌性小鼠，并用漂移变体A/Cal/09病毒攻击。与未接种疫苗的小鼠相比，无论性别如何，接种疫苗的成年但非老年小鼠在攻毒后的发病率更低，肺部病毒清除率更高。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。在小鼠中，疫苗效力的性别差异随着年龄的增长而减少。为了确定性类固醇在疫苗诱导的免疫应答中的作用，在接种疫苗前，切除成年小鼠的性腺，并在动物亚组中替换激素（雌性中的雌二醇和雄性中的睾酮）。雌性动物的疫苗诱导抗体应答因雌二醇而增加，雄性动物的疫苗诱导抗体应答因睾酮而减少。在小鼠和人类中，雌二醇升高对抗体应答和保护女性免受流感的益处随着年龄的增长而减少。
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.