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 naïve 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.

生物性别会影响适应性免疫反应，从而影响流感感染和疫苗效力。用2009 H1N1诱导的抗体反应，CD4 ⁺ T细胞和CD8 ⁺感染小鼠女性的T细胞记忆反应大于男性；然而，H1N1漂移变异病毒对两性均具有同样的保护，使其免受继发性攻击。为了测试雌性中较高的抗体是否足以抵抗流感，男性和女性用灭活的H1N1疫苗免疫，该疫苗主要诱导抗体介导的免疫。接种疫苗后，女性比男性具有更大的抗体反应和针对H1N1漂移变异病毒的攻击保护。源自接种疫苗的雌性的抗体在保护幼稚的雄性和雌性方面都比雄性的抗体更好，并且这种保护作用与提高的抗体特异性和对H1N1病毒的亲和力有关。Tlr7的表达接种过的雌性小鼠的B细胞比雄性小鼠更大，并且与Tlr7启动子区域的DNA甲基化减少，中和抗体更高，类别转换重组以及雌性抗体亲和力有关。Tlr7的删除减少了疫苗激发后抗体诱导的抗体反应和保护作用的性别差异，并且女性对男性的反应比男性具有更大的影响。综上所述，这些数据说明女性中更大的TLR7激活和抗体产生可提高疫苗接种抗流感的功效。