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

项目主任/首席调查员(最后、第一、中间)：Klein，Sabra L. 项目II：中国人对疫苗和流行性感冒病毒株免疫反应的性别差异 医护人员 摘要 流感的季节性流行对人类的公共健康构成了重大威胁，尽管 疫苗和抗病毒药物的可用性。流感疫苗的效力每年会有很大的不同 年份和疫苗的免疫原性或疫苗与疫苗之间的抗原匹配 流行的流感病毒株最常被指责为疗效低的原因。但是，宿主因素， 包括疫苗的性别和年龄，也可能是导致流感疫苗效果不佳的原因之一。 但这些都没有得到广泛的探索。成年雌性通常有更强的抗体反应 与男性相比，对一些抗原--包括流感疫苗--的抵抗力。这些差异 通常在性激素水平最高的生殖年龄段最明显。我们的 初步数据显示，女性(18-45岁)中和抗体滴度较高。 疫苗抗原，而不是抗原性变异病毒，这可能反映出更大的特异性 雌性的抗体反应。SADII研究项目2将调查#年的性别差异 18-45岁人群中接种流感疫苗的反应。我们会 量化先前存在的流感免疫力的性别差异，因为这可能有助于 接种疫苗后的性别差异。我们将用以下内容描述特定性别的差异 在一些不同的抗体反应中考虑荷尔蒙和遗传介质， 包括病毒中和活性、抗体亲和力和免疫球蛋白类开关重组。数字 将测定总B细胞和抗原特异性B细胞的转录活性和B细胞 产生抗体的B细胞的受体利用率将被量化。总而言之，在 SADII研究项目2将加强我们对性别在调节免疫中的作用的理解 对流感疫苗接种的反应并确定调节这些差异的性别差异机制 在成年人身上。如果处于育龄的女性产生抗体和记忆B细胞反应 比男性更高的效价和特异性，那么这应该会影响配方、剂量和预测 接种疫苗后的保护，类似于我们在接种疫苗时考虑年龄的方式 指导方针。 OMB编号0925-0001/0002(01/18修订版批准至2020年3月31日)页面续格式页面

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