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

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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.