Spike protein vaccine triggers systemic Th2 and Th17 inflammatory responses and pulmonary immunopathology following SARS-CoV-2 breakthrough infection

Abstract Vaccines have shown remarkable protection against COVID-19, but vaccination-enhanced respiratory disease (VAERD) following breakthrough infections poses safety concerns. SARS-CoV-2 Spike (SARS-2 S) protein subunit vaccines induced VAERD in hamsters, where aluminum adjuvant primed a Th2-biased immunization, resulting elevated type 2 pulmonary inflammation animals with infections. To further understand the potential risks and immunopathogenesis of VAERD, we immunized K18-hACE2 mice SARS-2 S presence CpG ODN adjuvants infected them lethal dose SARS-2. The vaccine robust antibody T cell responses, significantly reducing viral titers increasing host survival. However, infection, vaccinated exhibited severe airway immunopathology, dramatic increase eosinophils CD4 +T cells, Th2/Th17 cytokines lungs. Intracellular flow cytometric analysis showed systemic inflammatory response, prominently Our data show that aluminum/ODN elicit strong COVID-19 prime response may contribute to rapid onset cell-mediated immunopathology infection. results highlight need for additional studies elucidate COVID-19-associated improve formulations broad maximal safety. This research was supported part by grants from National Institutes Health (P20 GM130555-6610 R01 AI151139).