Immunization with MVA-based vaccines protects K18-hACE2 mice from SARS-CoV-2 infection-associated inflammatory lesions in brains.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known as the etiological agent of coronavirus disease 2019 (COVID-19). Extrapulmonary manifestations of COVID-19 have gained increasing recognition as significant contributors to disease severity and long-term complications. The aim of this study is to investigate the neuroprotective properties of vaccines based on modified Vaccinia Virus Ankara (MVA) against SARS-CoV-2 infection in K18-hACE2 mice using different immunization protocols. Animals received PBS, vector, recombinant MVA expressing native (S) or stabilized (ST) SARS-CoV-2 spike protein, nucleocapsid protein (N) or both ST and N protein twice, followed by infection with SARS-CoV-2 four weeks later. In further experiments, mice were immunized only once and infected two days (Emergency experiment) or four weeks (Prime experiment) later. Both the control groups and the animals immunized with vaccines expressing only N-protein showed mild to moderate, lymphohistiocytic meningoencephalitis, microgliosis and numerous virus antigen-positive neurons in the brains and to a lesser extent in the retinas. Groups immunized four weeks prior to infection with vaccines containing viral spike protein showed no or minimal inflammatory changes and no neuroinvasion. Animals infected two days after immunization showed milder lesions than unvaccinated control groups.