W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vaccine. 2022 Mar 8;40(11):1624-1633. doi: 10.1016/j.vaccine.2020.11.057. Epub 2020 Dec 5.
To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.
为了确定生物性别和年龄是否相互作用影响通用流感疫苗诱导的免疫，成年和老年雄性和雌性 C57BL/6 小鼠依次用嵌合血凝素（cHA）茎基 H1 疫苗免疫。成年小鼠产生了更多数量和质量的 H1 茎抗体，与其他组 1 但不是组 2 的流感病毒具有更高的交叉反应性，而老年小鼠则不然。该疫苗没有诱导中和或血凝抑制抗体，而是诱导抗体依赖性细胞毒性，成年小鼠比老年小鼠更强。接种疫苗的成年小鼠在 2009 年 H1N1 病毒攻击后比老年小鼠受到更好的保护，发病率更低，肺部病毒滴度更低。与男性相比，女性的免疫和保护随年龄的增长而下降更为明显，与成年女性相比，老年女性的免疫和保护下降通常是导致整体年龄相关显著差异的唯一比较。然而，女性中基于茎的免疫随年龄的降低与雌二醇的变化无关。为了确定成年人更好的抗体是否可用于保护老年小鼠，将来自接种成年小鼠的血清被动转移到未接种的性匹配老年小鼠中。即使使用来自年轻成年小鼠的转移血清，老年雌性小鼠的发病率仍高于老年雄性小鼠。这些数据表明，基于 cHA 的通用流感病毒疫苗诱导的免疫存在与性别相关的衰老影响，不能通过从小动物转移血清来逆转。缺乏对衰老对免疫的性别特异性影响的考虑可能会阻碍通用疫苗的研发。
