Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine

Ruoqiong Huang; Liyang Ying; Jiangmei Wang; Jie Xia; Yanjun Zhang; Haiyan Mao; Ruoyang Zhang; Ruoxi Zang; Zhenkai Le; Qiang Shu; Jianguo Xu

doi:10.3389/fimmu.2023.1139620

Non-spike and spike-specific memory T cell responses after the third dose of inactivated COVID-19 vaccine

Front Immunol. 2023 Apr 11:14:1139620. doi: 10.3389/fimmu.2023.1139620. eCollection 2023.

Authors

Affiliations

¹ Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.
² Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.

Abstract

Background: During the COVID-19 epidemic, vaccination has become the most safe and effective way to prevent severe illness and death. Inactivated vaccines are the most widely used type of COVID-19 vaccines in the world. In contrast to spike-based mRNA/protein COVID-19 vaccines, inactivated vaccines generate antibodies and T cell responses against both spike and non-spike antigens. However, the knowledge of inactivated vaccines in inducing non-spike-specific T cell response is very limited.

Methods: In this study, eighteen healthcare volunteers received a homogenous booster (third) dose of the CoronaVac vaccine at least 6 months after the second dose. CD4⁺ and CD8⁺ T cell responses against a peptide pool from wild-type (WT) non-spike proteins and spike peptide pools from WT, Delta, and Omicron SARS-CoV-2 were examined before and 1-2 weeks after the booster dose.

Results: The booster dose elevated cytokine response in CD4⁺ and CD8⁺ T cells as well as expression of cytotoxic marker CD107a in CD8⁺ T cells in response to non-spike and spike antigens. The frequencies of cytokine-secreting non-spike-specific CD4⁺ and CD8⁺ T cells correlated well with those of spike-specific from WT, Delta, and Omicron. Activation-induced markers (AIM) assay also revealed that booster vaccination elicited non-spike-specific CD4⁺ and CD8⁺ T cell responses. In addition, booster vaccination produced similar spike-specific AIM⁺CD4⁺ and AIM⁺CD8⁺ T cell responses to WT, Delta, and Omicron, indicting strong cross-reactivity of functional cellular response between WT and variants. Furthermore, booster vaccination induced effector memory phenotypes of spike-specific and non-spike-specific CD4⁺ and CD8⁺ T cells.

Conclusions: These data suggest that the booster dose of inactive vaccines broadens both non-spike-specific and spike-specific T cell responses against SARS-CoV-2.

Keywords: COVID-19; CoronaVac; T cell responses; inactivated vaccines; non-spike; spike.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes
COVID-19 Vaccines*
COVID-19* / prevention & control
Cytokines
Humans
Memory T Cells
SARS-CoV-2
Vaccines, Inactivated

Substances

sinovac COVID-19 vaccine
COVID-19 Vaccines
Cytokines
Vaccines, Inactivated

Grants and funding

This work was supported by the Health Commission of Zhejiang Province (2021KY188) and the National Natural Science Foundation of China (Grant No. 82070074 and 82272191).