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

医护人员对疫苗和流感病毒株的免疫反应存在性别差异

基本信息

批准号：
10213172
负责人：
Andrew S. Pekosz
金额：
$ 21.24万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10213172
关键词：
Address Adjuvant Adult Affect Age Age-Years Antibodies Antibody Avidity Antibody Response Antibody titer measurement Antigens Antiviral Agents B-Cell Antigen Receptor B-Lymphocytes Cessation of life Data Dose Exposure to Female Formulation Gender Genes Genetic Genetic Transcription Gonadal Steroid Hormones Guidelines Health Personnel Hormonal Human Immune response Immune system Immunity Immunoglobulin Class Switching Immunoglobulin G Immunoglobulin Switch Recombination Immunologics Individual Infection Influenza Influenza vaccination Integration Host Factors Libido Mediating Mediator of activation protein Memory B-Lymphocyte Plasmablast Play Population Principal Investigator Productivity Public Health Recording of previous events Reporting Research Research Personnel Research Project Grants Resources Role Seasons Serum Sex Differences Specificity Transcriptional Activation Universities Vaccination Vaccine Antigen Vaccines Variant Virus X Chromosome X Inactivation age difference age group base biological sex cohort gender difference hormone response element human disease human old age (65+)immunogenicity influenza epidemic influenza infection influenza virus strain influenza virus vaccine male neutralizing antibody programs reproductive response seasonal influenza serosurvey sex side effect social vaccination outcome vaccine acceptance vaccine access vaccine efficacy vaccine response vaccine trial

项目摘要

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

计划总监/首席研究员（最后，第一，中间）：Klein，Sabra L. 项目II：免疫复杂的性别差异，以疫苗和循环菌株的影响医护人员概括影响力的季节性情节对人类构成了重要的公共卫生威胁疫苗和抗病毒药的可用性。流感疫苗效率在一年中可能有很大差异年份以及疫苗的免疫原性或疫苗与抗原匹配循环影响力通常以低效率而变色。但是，宿主因素，包括疫苗的性别和年龄，也可能导致影响不佳的影响力疫苗效率但是这些并未得到广泛的探索。成年女性通常具有更强的抗体反应与男性相比，许多抗原（包括影响力疫苗）。这些差异在性骑士水平最高时，通常是在复制年份中最明显的。我们的初步数据说明，女性（18-45岁）会发展出更高的中和抗体滴度对疫苗抗原，但不适合抗原变异病毒，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将调查性别差异在18-45岁之间人类人群中对影响力疫苗接种的反应。我们将量化对影响力的免疫力的性别差异，因为这可能有助于大小疫苗接种后的性别差异。我们将以特定性别的差异来表征在许多不同的抗体反应中考虑激素和遗传介质，包括病毒中和活性，抗体亲和力和IgG类开关重组。数字将确定总和抗原特异性B细胞的转录活性和B细胞将量化产生抗体B细胞的受体利用。一起，研究 SADII研究项目2将增强我们对性别调节免疫作用的作用的理解对影响力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。如果生殖年龄的女性会产生抗体和记忆B细胞反应比男性更大的滴度和特异性，那么这应该告知公式，给药并预测疫苗后的保护，以类似于我们考虑疫苗年龄的方式指南。 OMB No. 0925-0001/0002（修订版01/18通过03/31/2020批准）页面延续格式页面