Dynamics of CD4(+) T-Cells and Neutralizing Antibody Responses to Three Consecutive Doses of Inactivated COVID-19 Vaccines in PLWH

BACKGROUND: Comprehensive characterization of safety and immune responses to vaccines is crucial for the prevention and treatment of COVID-19 among people living with HIV (PLWH). This study aimed to investigate the dynamic changes in SARS-CoV-2-specific CD4(+) T-cell subsets and neutralizing antibody after three consecutive doses of inactivated COVID-19 vaccines (BBIBP-CorV) among PLWH. METHODS: The blood samples were collected from 165 PLWH, including 66 PLWH in the 3-month interval between the second and third dose (cohort 1) and 99 PLWH in the 5-month interval (cohort 2). Blood collection for immunogenicity analysis was performed at 1-month post-2nd vaccination, pre-3rd vaccination, and within 2-month post-3rd vaccination. Wilcoxon matched-pairs signed-rank test was applied to compare the SARS-CoV-2-specific CD4(+) T cell subsets and neutralizing antibody level at different time points. The relationship among CD4(+) T-cells, Tregs subpopulations and SARS-CoV-2-specific neutralizing antibody level were evaluated with Spearman non-parametric correlation test. RESULTS: No serious adverse reactions were found among PLWH. After two-dose or three-dose inactivated COVID-19 vaccination, the absolute counts of CD4(+) T-cells and Tregs subpopulations (CD4(+)CD25(High)CD127(Low) Tregs, CD45RA(+) rTregs and CD45RO(+) eTregs) increased in two cohorts. Satisfactory SARS-CoV-2-specific neutralizing antibody responses to the third-dose vaccination were found in two cohorts, including significantly enhanced neutralizing antibody level and high neutralizing antibody seroconversion rate. In addition, SARS-CoV-2-specific neutralizing antibody level were positively associated with the absolute counts of CD4(+) T-cells and Tregs subpopulations as well as the frequency of CD45RO(+) eTregs in PLWH after three doses of vaccinations. CONCLUSION: The three doses of inactivated COVID-19 vaccination were both safe and effective to increase SARS-CoV-2-specific CD4(+) T-cells and neutralizing antibody in two PLWH cohorts with different inoculation intervals.