W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 2018 Dec 4;115(49):12477-12482. doi: 10.1073/pnas.1805268115. Epub 2018 Nov 19.
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 was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in the promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion of 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，这可能会影响流感感染和疫苗的效果。2009 年 H1N1 感染小鼠会诱导出抗体反应、CD4 T 细胞和 CD8 T 细胞记忆反应，这些反应在雌性小鼠中比在雄性小鼠中更强；然而，两种性别的小鼠在受到 H1N1 漂移变异病毒的二次攻击时都能得到同等的保护。为了测试女性体内更强的抗体是否足以预防流感，雄性和雌性小鼠都接种了一种灭活的 H1N1 疫苗，该疫苗主要诱导抗体介导的免疫。接种疫苗后，雌性小鼠的抗体反应和对 H1N1 漂移变异病毒的保护作用都比雄性小鼠更强。来自接种过疫苗的雌性小鼠的抗体比来自雄性小鼠的抗体更能有效地保护未感染的雄性和雌性小鼠，这种保护作用与抗体对 H1N1 病毒的特异性和亲和力的增加有关。与接种过疫苗的雄性小鼠相比，接种过疫苗的雌性小鼠的 B 细胞中 的表达更高，并且与 启动子区域的 DNA 甲基化减少、更高的中和抗体、类别转换重组和抗体亲和力有关。 的缺失减少了接种疫苗后对性别差异的抗体反应和保护作用，并且对雌性小鼠的影响大于对雄性小鼠的影响。综上所述，这些数据表明，女性 TLR7 激活和抗体产生的增加可提高流感疫苗的效果。
