Correlates of COVID-19 mRNA vaccine humoral immune responses in men living with HIV-1

Abstract It is important that people with HIV-1 (PWH) receive an FDA-approved vaccine for COVID-19. Because PWH are known to elicit less effective immune responses to other licensed vaccines, we assessed the humoral immune response to the novel COVID-19 mRNA vaccines in 139 fully vaccinated male participants (45 with HIV-1 [MWH] and 94 without HIV-1 [MWOH]) of the MACS/WIHS Combined Cohort Study. Levels of anti-nucleocapsid (N) and anti-spike 1 (S1) IgG and IgA were determined using ELISA and the MSD electro-chemiluminescence multiplex assay platform, to classify natural infection and vaccination status, and quantify binding IgG. Functional characterization of antibodies (Ab) was determined by measuring neutralizing Ab levels against WA, Delta, and Omicron strains, and immune complex complement activation capacity by complement component 3 (C3) deposition. We found that MWH who received two standard doses of mRNA vaccines had lower levels of vaccine-induced anti-S1 IgG and neutralizing Ab against the Washington, Delta, Omicron variants compared to MWOH, and these Ab titers were boosted in the context of natural SARS-CoV-2 infection for MWH. Interestingly, Ab in MWH promoted more potent C3 deposition. In all participants the Moderna mRNA-1273 vaccine induced significantly higher levels of binding IgG and neutralizing Abs against the variants. Importantly, preexisting immunity to the endemic human coronaviruses, participant age, and blood biochemical measurements correlated with these vaccine responses. Our data indicate that COVID-19 mRNA vaccine-induced humoral responses are impaired in MWH. Further studies are needed to define the long-term effects of this impairment on prevention and control of SARS-CoV-2 infection in MWH. Supported by grants from NIH: Pitt AIDS Research Training (PART) (NRSA 5T32AI065380-15) to DJT, NIH (NHLBI 5U01HL146208) and OAR/NHLBI Supplement (U01HL146208-03S2/S3), MWCCS Concepts X21033 and X20124, and NIH NIAID (R01-AI167711).