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Multiple vaccines against the Wuhan variant of SARS\u2010CoV\u20102 have been developed including a whole virion beta\u2010propiolactone\u2010inactivated 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\u2010CoV\u20102, the emergence of novel mutant variants raises concern over possible evasion of vaccine\u2010induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion\u2010based vaccine, against the Omicron variant. CoviVac\u2010immunized K18\u2010hACE2 Tg mice were protected against both prototype B.1.1 and BA.1\u2010like (Omicron) variants. Subsequently, vaccinated K18\u2010hACE2 Tg mice rapidly cleared the infection via cross\u2010reactive T\u2010cell responses and cross\u2010reactive, non\u2010neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS\u2010CoV\u20102 variants can be achieved by the orchestrated action of cross\u2010reactive T cells and non\u2010neutralizing antibodies.<\/jats:p>","DOI":"10.1002\/eji.202350664","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T06:12:34Z","timestamp":1702447954000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inactivated whole virion vaccine protects K18\u2010hACE2 Tg mice against the Omicron SARS\u2010CoV\u20102 variant via cross\u2010reactive T cells and nonneutralizing antibody responses"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-2087","authenticated-orcid":false,"given":"Andrey A.","family":"Kruglov","sequence":"first","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology Russian Academy of Sciences  Moscow Russia"},{"name":"Belozersky Institute of Physico\u2010Chemical Biology and Biological Faculty M.V. 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