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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

基本信息

批准号：
10581700
负责人：
Monica Gandhi
金额：
$ 24.23万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/10581700
关键词：
2019-nCoV Address Adult Age Antibodies Antibody Avidity Antibody Response Antibody titer measurement Attenuated Authorization documentation Automobile Driving B-Lymphocytes BLR1 gene Binding Biological Assay CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene COVID-19 COVID-19 pandemic COVID-19 vaccination COVID-19 vaccine Catabolism 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 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 Variant Virus Work Yellow Fever aging population antiretroviral therapy aspirate authority booster vaccine breakthrough infection cell mediated immune response cohort draining lymph node exhaustion experience immunoregulation indexing inflammatory marker insight neutralizing antibody neutralizing vaccine novel novel coronavirus phase III trial programmed cell death protein 1 public health relevance receptor expression recruit response sex vaccine distribution vaccine efficacy vaccine trial vaccine-induced immunity ward

项目摘要

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