Biological sex affects vaccine efficacy and protection against influenza in mice
Biological sex affects vaccine efficacy and protection against influenza in mice
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DOI：
10.1073/pnas.1805268115
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发表时间：
2018-12-04
影响因子：
11.1
通讯作者：
Klein, Sabra L.
中科院分区：
文献类型：
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作者：
Fink, Ashley L.;Engle, Kyrra;Klein, Sabra L.
生物性别影响适应性免疫反应，这可能影响流感感染和疫苗效力。用2009 H1N1感染小鼠诱导的抗体应答、CD 4（+）T细胞和CD 8（+）T细胞记忆应答在雌性中比雄性更大;然而，两种性别对H1N1漂移变异病毒的二次攻击的保护是相同的。为了测试雌性中更高的抗体是否足以保护免受流感，用灭活的H1N1疫苗免疫雄性和雌性，所述灭活的H1N1疫苗主要诱导抗体介导的免疫。接种疫苗后，女性比男性有更大的抗体反应和对H1N1漂移变异病毒攻击的保护。来自接种疫苗的女性的抗体在保护幼稚男性和女性方面比来自男性的抗体更好，并且这种保护与增加的抗体特异性和对H1N1病毒的亲合力相关。Tlr 7在接种疫苗的雌性B细胞中的表达高于雄性，并且与Tlr 7启动子区域中DNA甲基化降低、中和抗体升高、类别转换重组和雌性抗体亲合力相关。Tlr 7的缺失减少了疫苗诱导的抗体应答和攻击后保护的性别差异，并且对女性应答的影响大于男性。综上所述，这些数据表明，女性中更大的TLR 7活化和抗体产生提高了针对流感的疫苗接种的功效。
Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4(+) T cell and CD8(+) T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naive males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression of Tlr7 was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in the Tlr7 promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion of Tlr7 reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.