Immune response to COVID-19 vaccine in HIV infected men and women

HIV 感染男性和女性对 COVID-19 疫苗的免疫反应

基本信息

批准号：
10686994
负责人：
Robbie B Mailliard
金额：
$ 75.87万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10686994
关键词：
2019-nCoV Affect Anti-Retroviral Agents Antibodies Antibody Formation Antibody Response Antibody titer measurement Authorization documentation B-Lymphocytes Biological Markers CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes COVID-19 COVID-19 impact COVID-19 pandemic COVID-19 prevention COVID-19 vaccination COVID-19 vaccine Cell Count Cell physiology Cells Chronic Clinical Cohort Studies Data Data Set Disease Exhibits Female Genetic Transcription HIV HIV Infections Health Health Policy Healthcare Hepatitis B Vaccination IgG1 IgG3 Immune Immune System Diseases Immune response Immunity Immunization Immunocompetent Immunologic Deficiency Syndromes Immunologic Markers Individual Inflammation Influenza vaccination Interferon Type II Investigation Long-Term Effects Longitudinal Studies Machine Learning Measles Measurable Memory B-Lymphocyte Modeling Moderna COVID-19 vaccine Natural Killer Cells Outcome Participant Performance Persons Pfizer-BioNTech COVID-19 vaccine Phase Phenotype Prevention Public Health RNA vaccine Recommendation Resources SARS-CoV-2 B.1.1.7 SARS-CoV-2 B.1.351 Secondary Immunization Serology South African T-Cell Activation T-Lymphocyte TNF gene United States Vaccinated Vaccination Vaccinee Vaccines Viral Vector Woman authority cohort comorbidity coronavirus disease cytokine cytotoxic design immunogenicity male men multiple omics negative affect neutralizing antibody pathogen predictive marker response seroconversion success treatment trial vaccine immunogenicity vaccine response vaccine trial vector-based vaccine

项目摘要

ABSTRACT The CDC recommends that persons living with HIV (PWH) be vaccinated against SARS-CoV-2. However, there are minimal scientific data to support this important public health principle in relation to ongoing immune dysfunction and chronic comorbidities and the persistent HIV reservoir in antiretroviral treated (ART) PWH. We propose that a formal, comprehensive, longitudinal study in a well-characterized cohort of male and female PWH compared to HIV uninfected controls (HUC) is essential to assess the immunogenicity of COVID-19 vaccines in PWH. The MACS-WIHS Combined Cohort Study (MWCCS) is ideal for analyzing the interactive impact of chronic HIV infection on COVID-19 Pfizer and Moderna RNA-based vaccine immune responses to SARS-CoV-2 and the HIV reservoir. In Aim 1, we propose to conduct an in- depth analysis of antibody neutralizing function and B lymphocyte responses in 100 male PWH and 100 female vaccinated PWH, and 25 male and 25 female vaccinated HUC, from the MWCCS. In Aim 2, we will extensively characterize immune cell phenotypes, soluble markers, and functional cellular immune responses to SARS-CoV-2 vaccination in the participants from Aim 1 before and after vaccination. In Aim 3, we will evaluate the effects of COVID-19 vaccine on the persistent HIV reservoir (amount and composition, immune parameters) before and after immunization. Aim 4 applies machine learning approaches on the entire set of features quantified in Aims 1-3 to predict COVID-19 vaccine response outcomes and determine the critical parameters that influence vaccine responses. We believe that this study is unique, important, and critically timely for assessing the scientifically unprecedented, vaccine prevention phase of the COVID-19 pandemic in the context of HIV infection.

抽象的疾病预防控制中心建议对艾滋病毒（PWH）的人接种SARS-COV-2接种。然而，与正在进行的有关这一重要的公共卫生原则的科学数据最少免疫功能障碍和慢性合并症以及抗逆转录病毒治疗（ART）中持续的HIV储藏 PWH。我们建议在良好的男性队列中进行正式，全面的纵向研究与HIV未感染的对照（HUC）相比，女性PWH对于评估免疫原性至关重要 PWH中的Covid-19疫苗。 MACS-WIHS组合队列研究（MWCC）非常适合分析慢性HIV感染对Covid-19辉瑞和现代RNA的疫苗的互动影响对SARS-COV-2和HIV水库的免疫反应。在AIM 1中，我们建议进行一个内部抗体中和功能的深度分析和100个男性PWH和100的B淋巴细胞反应女性接种的PWH，25名男性和25名女性接种HUC，来自MWCC。在AIM 2中，我们将广泛表征免疫细胞表型，可溶性标记和功能性细胞免疫疫苗接种前后的参与者对参与者中SARS-COV-2疫苗接种的反应。在AIM 3中，我们将评估COVID-19疫苗对持续HIV储量的影响（数量和组成，，免疫参数）免疫前后。 AIM 4应用机器学习方法 AIMS 1-3中量化的整个特征集以预测Covid-19疫苗反应结果和确定影响疫苗反应的关键参数。我们认为这项研究是独一无二的重要且至关重要的是评估科学前所未有的预防疫苗在艾滋病毒感染的背景下，共同19-19大流行的阶段。