Sex differences in immune responses to vaccine and circulating strains of influenza in healthcare workers

项目负责人/主要研究者（最后，第一，中间）：Klein，Sabra L. 项目二：儿童对疫苗和流行性流感病毒株免疫反应的性别差异 医护人员 总结 流感的季节性流行对人类构成重要的公共卫生威胁， 疫苗和抗病毒药物的供应。流感疫苗的有效性每年都有很大差异， 年和疫苗的免疫原性或疫苗与 流行的流感病毒株最常被归咎于低疗效。然而，宿主因素， 包括疫苗的性别和年龄，也可能导致流感疫苗效力差 但这些尚未被广泛探索。成年雌性通常有更强的抗体反应 包括流感疫苗在内的多种抗原的免疫力。这些差异 通常在性激素水平最高的生育年龄最为明显。我们 初步数据表明，女性（18-45岁）产生较高的中和抗体滴度， 疫苗抗原，但不是抗原变异病毒，这可能反映了更大的特异性， 雌性的抗体反应SADII研究项目2将调查 在年龄在18-45岁之间的个体的人类队列中对流感疫苗接种的应答。我们将 量化预先存在的流感免疫力的性别差异，因为这可能导致 接种疫苗后的性别差异。我们将描述性别特异性差异， 考虑激素和遗传介质，在许多不同的抗体反应， 包括病毒中和活性、抗体亲合力和IgG类别转换重组。数量 将测定总的和抗原特异性的B细胞的转录活性和B细胞 产生抗体的B细胞的受体利用将被定量。总的来说， SADII研究项目2将提高我们对性在调节免疫系统中的作用的理解。 对流感疫苗接种的反应，并确定介导这些差异的性别特异性机制 在成年人中。如果育龄女性产生抗体和记忆B细胞反应， 滴度和特异性高于雄性，则这应告知制剂、给药和预测 接种疫苗后的保护，类似于我们在接种疫苗时考虑年龄 指南 OMB编号0925-0001/0002（2018年1月批准至2020年3月31日修订版）页码续页格式页码

Program Director/Principal Investigator (Last, First, Middle): Klein, Sabra L. PROJECT II: Sex differences in immune responses to vaccine and circulating strains of influenza in healthcare workers Summary Seasonal epidemics of influenza pose important public health threats to humans despite the availability of vaccines and antivirals. Influenza vaccine efficacy can vary significantly from year to year and the immunogenicity of the vaccine or the antigenic match between the vaccine and circulating influenza strains are most often blamed for the low efficacy. However, host factors, including the sex and age of the vaccine, may also be contributing to poor influenza vaccine efficacy but these have not been explored extensively. Adult females often have stronger antibody responses to a number of antigens – including influenza vaccines - when compared to males. These differences are often most pronounced during their reproductive years when sex hormone levels are highest. Our preliminary data illustrate that females (18-45 years of age) develop higher neutralizing antibody titers to a vaccine antigen, but not to a antigenic variant virus, which may reflect the greater specificity of the female’s antibody response. The SADII Research Project 2 will investigate sex differences in response to influenza vaccination in a human cohort of individuals between the ages of 18-45. We will quantify sex differences in pre-existing immunity to influenza, as this may contribute to the magnitude of the sex differences after vaccination. We will characterize sex-specific differences, with consideration of hormonal and genetic mediators, in a number of different antibody responses, including virus neutralizing activity, antibody avidity, and IgG class switch recombination. The number of total and antigen-specific B cells will be determined and the transcriptional activity and B cell receptor utilization of the antibody producing B cells will be quantified. Together, the studies in the SADII Research Project 2 will enhance our understanding of the role of sex in modulating the immune response to influenza vaccination and identify sex-specific mechanisms mediating those differences in adults. If females of reproductive ages develop antibody and memory B cell responses that are of greater titer and specificity than males, then this should inform the formulation, dosing, and predicted protection following vaccination, in a manner similar to our consideration of age in vaccination guidelines. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page