Altered SARS-CoV-2 Vaccine Responses in People Living with HIV: Roles of ART, HIV-Specific T-Cells, and CD4 Deficiency 9309

Abstract Description This study investigated how human immunodeficiency virus (HIV) and associated immunosuppression influenced development of post-vaccination immunity to SARS-CoV-2. among. Twenty-two people living with HIV (PLWH) and 30 healthy donors (HDs) were recruited from the Greater New Orleans Area of Louisiana, with samples collected 21–378 days following mRNA SARS-CoV-2 vaccination (Pfizer or Moderna). We analyzed plasma and cellular samples using systems serology approaches together with T-cell (Tc) surface marker profiling for activation & subset phenotyping following SARS-CoV-2 spike or HIV-1 gag peptide pool stimulation. Lentiviral pseudovirus neutralization assays were found to be compromised by antiretroviral therapy (ART) drugs in patients’ plasma. Isotype prevalence targeting spike and receptor-binding domain epitopes were altered post-vaccination in PLWH compared to HDs. While memory phenotypes were similar between PLWH and HDs, the durability & quality of CD4 but not CD8 Tc responses were reduced in PLWH. Notably, altered spike-specific immune responses correlated with CD4 and CD8 Tc responses to HIV-1 gag peptide. In conclusion, primary SARS-CoV-2 vaccination in immunocompetent PLWH generates comparable CD8 T-cell memory and spike-specific antibodies relative to healthy controls. However, CD4 T-cell and antibody responses were altered in PLWH post-vaccination based on CD4 immunodeficiency, ART, and HIV-specific Tc activation Funding Sources Funding for this study was provided under NIH Project U54CA260581-01 Topic Categories Viral Immunology (VIR)