Influenza virus strains expressing SARS-CoV-2 receptor binding domain protein confer immunity in K18-hACE2 mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), rapidly spread across the globe in 2019. With the emergence of the Omicron variant, COVID-19 shifted into an endemic phase. Given the anticipated rise in cases during the fall and winter seasons, the strategy of implementing seasonal booster vaccines for COVID-19 is becoming increasingly valuable to protect public health. This practice already exists for seasonal influenza vaccines to combat annual influenza seasons. Our goal was to investigate an easily modifiable vaccine platform for seasonal use against SARS-CoV-2. In this study, we evaluated the genetically modified influenza virus Delta NA(RBD) as an intranasal vaccine candidate for COVID-19. This modified virus was engineered to replace the coding sequence for the neuraminidase (NA) protein with a membrane-anchored form of the receptor binding domain (RBD) protein of SARS-CoV-2. We designed experiments to assess the protection of Delta NA(RBD) in K18-hACE2 mice using lethal (Delta) and non-lethal (Omicron) challenge models. Controls of COVID-19 mRNA vaccine and our lab's previously described intranasal virus like particle vaccine were used as comparisons. Immunization with Delta NA(RBD) expressing ancestral RBD elicited high anti-RBD IgG levels in the serum of mice, high anti-RBD IgA in lung tissue, and improved survival after Delta variant challenge. Modifying Delta NA(RBD) to express Omicron variant RBD shifted variant-specific antibody responses and limited viral burden in the lungs of mice after Omicron variant challenge. Overall, this data suggests that Delta NA(RBD) could be an effective intranasal vaccine platform that generates mucosal and systemic immunity towards SARS-CoV-2.