Evaluation of the Impact of HIV Status on the Immune Response to mRNA COVID-19 Vaccines

评估 HIV 状态对 mRNA COVID-19 疫苗免疫反应的影响

• 批准号: 10481408
• 负责人: Monica Gandhi
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10481408
• 关键词: 2019-nCoV; Address; Adult; Antibodies; Antibody Avidity; Antibody Response; Antibody titer measurement; Attenuated; Automobile Driving; B-Lymphocytes; BLR1 gene; Binding; Biological Assay; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cell Count; Cells; Cellular Immunity; Clinic; Clinical; Data; Defect; Development; Dose; Effectiveness; Failure; Functional disorder; Future; HIV; HIV Infections; HIV Seronegativity; Hepatitis B Vaccination; Immune; Immune response; Immunity; Immunoglobulin G; Immunologic Markers; Impact evaluation; Impairment; Individual; Infection; Inflammation; Inflammatory; Intercept; Investigation; Linear Models; Measures; Mediating; Mediator of activation protein; Memory B-Lymphocyte; Messenger RNA; Nucleocapsid; OX40; Participant; Patients; Peptides; Persons; Plasmablast; Population; Provider; Public Health; RNA vaccination; Recording of previous events; Recovery; Reporting; Research Infrastructure; Research Personnel; SARS-CoV-2 B.1.617.2; SARS-CoV-2 immunity; SARS-CoV-2 infection; Safety; Secondary Immunization; Serology; Site; South African; Structure of germinal center of lymph node; T cell response; T memory cell; T-Cell Activation; T-Lymphocyte; Time; Tryptophan 2,3 Dioxygenase; Vaccination; Vaccines; Virus; Work; Yellow Fever; aging population; antiretroviral therapy; base; booster vaccine; breakthrough infection; cell mediated immune response; cohort; draining lymph node; exhaustion; experience; indexing; inflammatory marker; insight; neutralizing antibody; neutralizing vaccine; novel; novel coronavirus; phase III trial; programmed cell death protein 1; public health relevance; receptor; recruit; response; sex; vaccine distribution; vaccine efficacy; vaccine trial; vaccine-induced immunity; ward

PROJECT SUMMARY/ ABSTRACT At this point in the COVID-19 pandemic, with vaccine roll-out ongoing, one of the most urgent questions facing people living with HIV (PLWH) and their providers is whether HIV modulates the immune response to and subsequent effectiveness of the SARS-CoV-2 vaccines. Unfortunately, phase 3 trials for all three of the U.S.-authorized vaccines did not report HIV specific data and/or did not include enough PLWH to examine the impact of HIV infection on vaccine efficacy. PLWH might plausibly experience a less durable SARS-CoV-2 specific neutralizing antibody (NAb) response to a SARS-CoV-2 vaccine, as has been seen in response to vaccines for other infections. This lack of durable NAb responses may be mediated by inflammatory state of HIV infection that persists despite adequate suppressive antiretroviral therapy (ART), T cell exhaustion, and/or lower CD4/CD8 ratios. Our preliminary work in the UCSF Long-term Impact of Infection with Novel Coronavirus (LIINC) COVID-19 recovery study has demonstrated waning antibody responses but stable CD4+ and CD8+ T cell responses among HIV-negative individuals recovering from natural SARS-CoV-2 infection. However, surrogate virus neutralization titers and IgG concentrations were lower among PLWH compared to adults without HIV following mRNA vaccination, raising concerns that PLWH might have a diminished humoral response to vaccination. Whether PLWH mount less durable humoral and cell-mediated immune responses to COVID-19 vaccines than those without HIV is largely unknown, including the mechanisms of these differences, although this information could inform clinical strategies, including additional boosters or safety measures after vaccination. This proposal will answer two vital questions about the response to vaccination among PLWH. Aim 1 will provide novel, urgently needed insights into how the SARS-CoV-2 neutralizing antibody response to a cultured B.1.617.2 (delta) variant, IgG concentration, and antibody magnitude and durability could differ by HIV status over time following mRNA-based SARS-CoV-2 vaccination, including following boosters. Aim 2 will examine T cell memory responses and germinal center development generated by mRNA-based SARS-CoV-2 vaccination among PLWH compared to those without HIV out to a year following vaccination. Harnessing, the research infrastructure of the UCSF CFAR, the LIINC study, and a large, aging population of PLWH served by the Ward 86 clinic, this analysis will leverage an ongoing cohort to address whether PLWH mount attenuated immune responses to COVID-19 vaccines. Such data will inform clinical and public health responses, including the need for additional vaccine doses or safety strategies for PLWH during COVID-19.

项目摘要/摘要 此时，在COVID-19大流行中，疫苗正在进行，这是最紧迫的问题之一 面对艾滋病毒（PLWH）及其提供者的人是艾滋病毒是否调节免疫反应 SARS-COV-2疫苗的随后有效性。不幸的是，这三个阶段的第三阶段试验 美国授权的疫苗未报告特定数据和/或不包括足够的PLWH来检查 艾滋病毒感染对疫苗功效的影响。 PLWH可能会出现耐用的SARS-COV-2特异性中和抗体（NAB）响应的耐用性较低 如响应其他感染的疫苗所见，SARS-COV-2疫苗是对其他感染的。缺乏耐用的 NAB反应可能是通过炎症状态介导的，尽管艾滋病毒感染的炎症状态仍然足够 抑制性抗逆转录病毒疗法（ART），T细胞耗尽和/或较低的CD4/CD8比率。我们的初步工作 在UCSF中，新型冠状病毒（LIINC）COVID-19恢复研究的长期影响已有 显示出衰弱的抗体反应，但在HIV阴性中稳定的CD4+和CD8+ T细胞反应 从天然SARS-COV-2感染中恢复的个体。但是，替代病毒中和滴度和 与mRNA疫苗接种后没有HIV的成年人相比，PLWH的IgG浓度较低， 引起人们对PLWH可能对疫苗接种的体液反应减少的担忧。是否plwh坐骑 与没有HIV的疫苗相比 尽管这些信息可以告知临床，但在很大程度上未知，包括这些差异的机制 策略，包括疫苗接种后的其他助推器或安全措施。 该提议将回答有关PLWH中对疫苗接种反应的两个至关重要的问题。目标1 将为SARS-COV-2中和抗体的反应如何提供新颖，迫切需要的见解 培养的B.1.617.2（Delta）变体，IgG浓度和抗体幅度和耐用性可能因HIV而异 基于mRNA的SARS-COV-2疫苗接种，包括以下助推器，随着时间的推移状态。目标2将 检查基于mRNA的SARS-COV-2产生的T细胞记忆反应和生发中心发育 与没有艾滋病毒的患者相比，PLWH之间的疫苗接种与疫苗接种后一年相比。利用， UCSF CFAR，LIINC研究和大量老化的PLWH的研究基础设施 由Ward 86诊所服务，该分析将利用持续的队列来解决PLWH MOUNT是否 对COVID-19疫苗的免疫反应减弱。这些数据将为临床和公共卫生提供信息 反应，包括在19日期间需要额外的疫苗剂量或PLWH的安全策略。