Suboptimal Fc-mediated antibody responses in people with vs. without HIV after COVID-19 vaccinations 2174

Abstract Description The COVID-19 pandemic has resulted in millions of excess mortality worldwide. People with HIV-1 (PWH) are among the immunocompromised populations with higher rates of hospitalization and increased risk of persistent SARS-CoV-2 replication, even with successful antiretroviral therapy (ART). They also exhibit impaired immune responses to other respiratory infections and poor responses to influenza and pneumococcal vaccines. Hence, we postulate that PWH similarly mount suboptimal responses to the COVID-19 vaccines. This study evaluated SARS-CoV-2- and HIV-1-specific antibodies in PWH on ART and people without HIV-1 (PWOH), within one year after the third dose of LNP-mRNA COVID-19 vaccines. Using multiplex bead binding antibody assays, we measured the antibody levels and capacities to bind complement and Fc receptor. SARS-CoV-2-specific Ig titers were elevated in the PWH vs. PWOH groups, but the Fc activities, as indicated by C1q and FcgRIIIa binding, were lower in the PWH vs. PWOH group. In the PWH group, reduced Fc potencies were also noted for antibodies against HIV-1 gp120 vs. SARS-CoV-2 spike. While further analyses of other Fc properties and functions are on-going, our data thus far point to specific curtailments in the Fc functionalities of SARS-CoV-2- and HIV-1-specific antibodies generated during chronic HIV-1 infection that may contribute to impaired immune responses against these viruses in PWH. Topic Categories Vaccines and Immunotherapy (VAC)