Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females

被引：127

作者：

Potluri, Tanvi ^{[1
]}

Fink, Ashley L. ^{[1
,4
,5
]}

Sylvia, Kristyn E. ^{[1
]}

Dhakal, Santosh ^{[1
]}

Vermillion, Meghan S. ^{[1
,2
]}

vom Steeg, Landon ^{[1
]}

Deshpande, Sharvari ^{[1
]}

Narasimhan, Harish ^{[1
]}

Klein, Sabra L. ^{[1
,3
]}

机构：

[1] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA

[2] Johns Hopkins Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21201 USA

[3] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA

[4] Coll St Benedict, Biol Dept, Collegeville, MN 56321 USA

[5] St Johns Univ, Collegeville, MN 56321 USA

来源：

NPJ VACCINES | 2019年 / 4卷 / 1期

关键词：

ANTIBODY-RESPONSE; IMMUNE-RESPONSE; CYTOKINE LEVELS; A H1N1; TESTOSTERONE; WOMEN;

D O I：

10.1038/s41541-019-0124-6

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：12