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Vaccine-induced protection against SARS-CoV-2 requires IFN-γ-driven cellular immune response
Xiaolei Wang1,2, Terrence Tsz-Tai Yuen3, Ying Dou1
1School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
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.
Insights
The mRNA vaccine BNT162b2 provides protection against COVID-19 variants by inducing cellular immunity. This cellular immunity, marked by interferon-gamma production, is crucial for protection when antibody immunity is evaded.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- COVID-19 pandemic control relies on mass vaccination.
- SARS-CoV-2 Omicron variants evade immunity from vaccination or prior infection.
- The role of cellular immunity against immune-evasive variants requires investigation.
Purpose of the Study:
- To determine if the mRNA vaccine BNT162b2 induces anti-viral cellular immunity against SARS-CoV-2 variants.
- To assess the protective efficacy of BNT162b2 in a model lacking humoral immunity.
- To investigate the contribution of cellular immunity to protection against Omicron sub-variants.
Main Methods:
- Utilized K18-hACE2 transgenic B-cell deficient (μMT) mice.
- Administered the mRNA vaccine BNT162b2 to mice.
- Challenged vaccinated mice with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants.
- Assessed cellular immunity, focusing on Interferon-gamma (IFN-γ) production.
Main Results:
- BNT162b2 vaccination conferred robust protective immunity in μMT mice.
- Protection was attributed to cellular immunity, evidenced by significant IFN-γ production.
- Vaccinated μMT mice showed boosted cellular responses upon challenge with Omicron BA.1 and BA.5.2.
Conclusions:
- The mRNA vaccine BNT162b2 induces significant protective immunity independent of antibody production.
- Cellular immunity plays a critical role in combating SARS-CoV-2 variants that evade humoral immunity.
- These findings underscore the importance of cellular immunity in the context of evolving SARS-CoV-2 variants.
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