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

• Published in: Nature communications Vol. 14; no. 1; p. 3440
• Main Authors: Wang, Xiaolei, Yuen, Terrence Tsz-Tai, Dou, Ying, Hu, Jingchu, Li, Renhao, Zeng, Zheng, Lin, Xuansheng, Gong, Huarui, Chan, Celia Hoi-Ching, Yoon, Chaemin, Shuai, Huiping, Ho, Deborah Tip-Yin, Hung, Ivan Fan-Ngai, Zhang, Bao-Zhong, Chu, Hin, Huang, Jian-Dong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.06.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/21; 13/31; 13/51; 14; 38/39; 38/91; 45/88; 631/250/1619/40; 631/250/2152/1566; 631/250/590; 631/326/596/4130; 64/110; Animals; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antiviral agents; BNT162 Vaccine; Cell-mediated immunity; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Humanities and Social Sciences; Humans; Humoral immunity; Immune response; Immune response (cell-mediated); Immune system; Immunity; Immunity, Cellular; Interferon-gamma; Lymphocytes; Lymphocytes B; Lymphocytes T; Mice; mRNA; multidisciplinary; Pandemics; Robustness; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Transgenic mice; Vaccines; Viral diseases; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39096-y

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. Protective immunity against SARS-CoV-2 relies on both antibodies and a T cell dependent response, however, direct experimental evidence for the contribution of cellular immunity is limited. Here authors present a mouse model that is susceptible to SARS-CoV-2 and lacks B cells to demonstrate the emergence of efficient cellular immune response against SARS-CoV-2 upon vaccination or viral challenge.