Immune Response to SARS-CoV-2 RNA Vaccination in HIV-Positive Individuals

Research presented at the Conference on Retroviruses and Opportunistic Infections (CROI) dives into the immune response to SARS-CoV-2 RNA vaccination in people with HIV (PWH) who are undergoing antiretroviral therapy (ART) reveals differences based on prior infection status. Specifically, PWH who had previously contracted SARS-CoV-2 showed enhanced non-neutralizing antibody functions tied to innate immunity, leading to a broader immune defense against the virus, including potent responses to Omicron variants, after receiving an RNA vaccine based on the Wuhan strain.

The study found that vaccination elicited neutralizing antibodies against the spike protein in both groups. However, those with a history of both HIV and COVID-19 showed significantly higher levels and longer-lasting neutralizing antibodies, particularly against the Omicron BA.1 and BA.2 subvariants. Additionally, both groups developed non-neutralizing antibody responses (ADCC and ADCP), but the ADCC response was notably stronger in the HIV-positive/COVID-positive group. Despite a sustained rise in T-cells and monocytes after vaccination in both groups, there was no corresponding increase in T-cell-specific responses to HIV Gag or Nef proteins.

The study involved 44 individuals with HIV on ART, including 24 with a prior SARS-CoV-2 infection and 20 without. It tracked immune responses at four points: before the first and second vaccine doses and 3 and 6 months after the second dose. The research measured various immune responses, including the levels of the total spike, receptor-binding domain, and nucleocapsid antibodies, neutralizing antibody levels, Fc-mediated functions (such as antibody-dependent cellular cytotoxicity, complement deposition, and phagocytosis), as well as cell-mediated immune responses specific to both SARS-CoV-2 and HIV and the activation status of T cells and monocytes.

The effect of a prior SARS-CoV-2 infection on both the antibody and cell-mediated immune responses following a 2-dose regimen of SARS-CoV-2 RNA vaccine in people with HIV on ART remains unclear. Additional research is required on the impact of vaccine-triggered, Fc-mediated innate immune responses on the risk of reinfection and disease progression remains to be fully understood, indicating the need for further research in this area.

Reference

Azzoni L, Tietien I, Liu Q, et. al. 393. Prior COVID-19 Alters Antibody Function in ART-Suppressed PWH Receiving SARS- CoV-2 Vaccination. Poster #393 presented at CROI 2024. March 3-6, 2023. Denver, CO.