Impact of CD4+ T cell and TCR repertoires on SARS-CoV-2-Specific antibody responses in PLWH following COVID-19 vaccination

In people living with human immunodeficiency virus (HIV, PLWH), the coronavirus disease 2019 (COVID-19) vaccine often results in a limited humoral immune response. While a reduced absolute CD4+ T cell count is a known factor, other determinants remain unclear. To investigate variables influencing the differential antibody response to the COVID-19 vaccine in PLWH, 43 HIV-1/AIDS patients receiving antiretroviral therapy (ART) and 2 doses of the COVID-19 vaccine were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) levels and neutralizing antibody (NAb) titers. A retrospective analysis was also performed, examining immune reconstitution and epidemiological history, including annual CD4+ T-cell counts and the duration of HIV-1 infection. To further elucidate the role of CD4+ T cells in the antibody response to the COVID-19 vaccine, next-generation sequencing was used to analyze the T cell receptor (TCR) profiles of CD4+ T cells from twelve representative individuals. The results showed that the SARS-CoV-2-specific antibody response in PLWH was not solely determined by the current CD4+ T cell count, the progression of immune reconstitution and the TCR profile of CD4+ T cells also played significant roles. These findings provide critical insights into the multifaceted roles of CD4+ T cells in SARS-CoV-2-specific antibody responses in PLWH following COVID-19 vaccination.