Inactivated whole virion vaccine protects K18‐hACE2 Tg mice against the Omicron SARS‐CoV‐2 variant via cross‐reactive T cells and nonneutralizing antibody responses.

COVID‐19 is a systemic inflammatory disease initiated by SARS‐CoV‐2 virus infection. Multiple vaccines against the Wuhan variant of SARS‐CoV‐2 have been developed including a whole virion beta‐propiolactone‐inactivated vaccine based on the B.1.1 strain (CoviVac). Since most of the population has been vaccinated by targeting the original or early variants of SARS‐CoV‐2, the emergence of novel mutant variants raises concern over possible evasion of vaccine‐induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion‐based vaccine, against the Omicron variant. CoviVac‐immunized K18‐hACE2 Tg mice were protected against both prototype B.1.1 and BA.1‐like (Omicron) variants. Subsequently, vaccinated K18‐hACE2 Tg mice rapidly cleared the infection via cross‐reactive T‐cell responses and cross‐reactive, non‐neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS‐CoV‐2 variants can be achieved by the orchestrated action of cross‐reactive T cells and non‐neutralizing antibodies. [ABSTRACT FROM AUTHOR]