Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response

Xiaolei Wang, Terrence Tsz-Tai Yuen, Ying Dou, Jingchu Hu, Renhao Li, Zheng Zeng, Xuansheng Lin, Huarui Gong, Celia Hoi-Ching Chan, Chaemin Yoon, Huiping Shuai, Deborah Tip-Yin Ho, Ivan Fan-Ngai Hung, Bao-Zhong Zhang (), Hin Chu () and Jian-Dong Huang ()
Additional contact information
Xiaolei Wang: The University of Hong Kong
Terrence Tsz-Tai Yuen: The University of Hong Kong
Ying Dou: The University of Hong Kong
Jingchu Hu: The University of Hong Kong
Renhao Li: The University of Hong Kong
Zheng Zeng: The University of Hong Kong
Xuansheng Lin: The University of Hong Kong
Huarui Gong: The University of Hong Kong
Celia Hoi-Ching Chan: The University of Hong Kong
Chaemin Yoon: The University of Hong Kong
Huiping Shuai: The University of Hong Kong
Deborah Tip-Yin Ho: The University of Hong Kong
Ivan Fan-Ngai Hung: The University of Hong Kong
Bao-Zhong Zhang: The University of Hong Kong
Hin Chu: The University of Hong Kong
Jian-Dong Huang: The University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (μMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated μMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2.

Date: 2023
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DOI: 10.1038/s41467-023-39096-y

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