The Third dose of CoronVac vaccination induces broad and potent adaptive immune responses that recognize SARS-CoV-2 Delta and Omicron variants

ABSTRACT

The waning humoral immunity and emerging contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants resulted in the necessity of the booster vaccination of coronavirus disease 2019 (COVID-19). The inactivated vaccine, CoronaVac, is the most widely supplied COVID-19 vaccine globally. Whether the CoronaVac booster elicited adaptive responses that cross-recognize SARS-CoV-2 variants of concern (VoCs) among 77 healthy subjects receiving the third dose of CoronaVac were explored. After the boost, remarkable elevated spike-specific IgG and IgA responses, as well as boosted neutralization activities, were observed, despite 3.0-fold and 5.9-fold reduced neutralization activities against Delta and Omicron strains compared to that of the ancestral strain. Furthermore, the booster dose induced potent B cells and memory B cells that cross-bound receptor-binding domain (RBD) proteins derived from VoCs, while Delta and Omicron RBD-specific memory B cell recognitions were reduced by 2.7-fold and 4.2-fold compared to that of ancestral strain, respectively. Consistently, spike-specific circulating follicular helper T cells (cTfh) significantly increased and remained stable after the boost, with a predominant expansion towards cTfh17 subpopulations. Moreover, SARS-CoV-2-specific CD4⁺ and CD8⁺ T cells peaked and sustained after the booster. Notably, CD4⁺ and CD8⁺ T cell recognition of VoC spike was largely preserved compared to the ancestral strain. Individuals without generating Delta or Omicron neutralization activities had comparable levels of CD4⁺ and CD8⁺ T cells responses as those with detectable neutralizing activities. Our study demonstrated that the CoronaVac booster induced broad and potent adaptive immune responses that could be effective in controlling SARS-CoV-2 Delta and Omicron variants.

KEYWORDS:

• COVID-19 vaccine
• booster
• coronavac
• neutralization
• T cell responses

Acknowledgements

The authors thank all vaccine recipients for providing serum samples. C. W. and H. S. designed the study. Y. C., L. C., Y. T. recruited the patients. M. L., Y. W. and J. N. processed the blood samples, M. M., L. M. and Y. S. performed cellular analysis. Y. L. performed the antibody assay. Y. S. and C. L. analysed and interpreted the data. Y. C. and L. C. wrote the manuscript. All the authors revised the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University [grant number 2021-LCYJ-PY-09], Nanjing Important Science & Technology Specific Projects [grant number 2021-11005], Nanjing Medical Science and Technique Development Foundation [grant numbers QRX17141 and YKK19056], Social Development Foundation of Jiangsu Province [grant number BE2021739].