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

Abstract

Wenhui Zhang,1,2 Shourong Liu,1 Liangbin Miao,3 Ai Fu,3 Jianfeng Bao,4 Liping Zheng,2 Er Li,2 Jianhua Yu,1,* Yi Wang1,3,* 1Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Hepatology, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhua Yu, Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email [email protected] Yi Wang, Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email [email protected]: 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+CD25HighCD127Low 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.Keywords: CD4+ T-cells, neutralizing antibody, inactivated COVID-19 vaccines, PLWH

Keywords

• cd4+ t-cells
• neutralizing antibody
• inactivated covid-19 vaccines
• plwh