An Integrative Analysis of the Immune Features of Inactivated SARS-CoV-2 Vaccine (CoronaVac)

Abstract

Currently, an inactivated vaccine has been widely used with encouraging results as a prophylactic agent against COVID-19 infection, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. However, in vitro SARS-CoV-2 vaccine-specific immune features remain elusive, hindering the promotion of a third dose of the vaccine. Here, we present a detailed in vitro immune cellular response and large-scale multi-omics analysis for peripheral blood mononuclear cells (PBMCs) from participants vaccinated with CoronaVac (Sinovac Life Sciences, Beijing, China) and recovered participants from COVID-19. The mean titers of SARS-CoV-2 serum-neutralizing antibodies were significantly increased after the boosting immunization (Day 45) compared to the unimmunized state. We observed that type-1 helper T cells (Th1) tended to dominate after the first dose of vaccine, while humoral immune responses became dominant after the second dose due to the activation of type-2 helper T cell (Th2), memory B cells, and plasmablasts. T follicular helper cells (Tfh) involved in antibody production were activated after the first dose and were maintained for the observed time points. Single-cell RNA sequencing of PBMCs revealed specific changes in cell compositions and gene expression in immunized participants. Multi-omics analysis also demonstrated that CoronaVac-specific serum proteins, plasma metabolites, and plasma lipid changes were skewed to those changes in convalescent patients. Collectively, we provide a comprehensive understanding of CoronaVac-specific in vitro immune features.

Serum peptidome profiles immune response of COVID-19 Vaccine administration

“…A clinical study focusing on the immunology of 71 confirmed COVID-19 cases found that complement component C1q dropped in severe COVID-19 patients significantly compared with mild-ill patients ( 31 ). The CoronaVac-induced regulation of complement C1q subcomponent was also detected by Jiang et al ( 19 ).…”

“…Since the cytokines were measured from serum without the knowledge of production cells and were only measured on two days, further information on the role of the cytokines in CoronaVac vaccination cannot be obtained in this study. Zhao et al (18) and Jiang et al (19) have studied the regulation of cytokines and lymphocytes induced by CoronaVac in a comprehensive way in their respective studies. Jiang et al characterized the lymphocyte subpopulations before and after vaccination, and found that after the second vaccination, CD8+ cytotoxic T cell levels decreased and the serum NAbs titers increased (19), in consistent with our results, which can suggest a balance between cellular and humoral immune responses dominating at early and late stages of vaccination, respectively.…”

“…Jiang et al. detected the changes of mannan-binding lectin serine proteases induced by CoronaVac ( 19 ). The reduction of MBL serum level or MBL protein concentration has been observed in SARS patients compared to healthy people ( 45 , 47 ).…”

“…( 18 ) and Jiang et al. ( 19 ) have studied the regulation of cytokines and lymphocytes induced by CoronaVac in a comprehensive way in their respective studies. Jiang et al.…”

“…Recently, Zhao et al reported the humoral and cellular immune responses of 136 participants activated by two-dose of CoronaVac after 1, 3, 6, and 12 moths (18). Jiang et al reported the immune features of CoronaVac based on 13 healthy people and 12 people that recovered from COVID-19 infection (19). Although pharmaceutical companies have reported the efficacy, safety and immunogenicity of COVID-19 vaccines based on laboratory studies and clinical trials, additional vaccine evaluation is needed to better understand the effect of COVID-19 vaccines on human beings, and new strategies for the evaluation of immune response against vaccines are needed.…”