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

tetano

Editor, Senior Moderator
Front Immunol


. 2026 Mar 10:17:1788665.
doi: 10.3389/fimmu.2026.1788665. eCollection 2026.
Immunization with MVA-based vaccines protects K18-hACE2 mice from SARS-CoV-2 infection-associated inflammatory lesions in brains

Małgorzata Rosiak[SUP] 1 2 [/SUP], Sabrina Clever[SUP] 3 [/SUP], Eva Leitzen[SUP] 1 [/SUP], Georg Beythien[SUP] 1 2 [/SUP], Lukas Mathias Michaely[SUP] 1 [/SUP], Sandra Lockow[SUP] 1 [/SUP], Lisa Allnoch[SUP] 1 [/SUP], Malgorzata Ciurkiewicz[SUP] 1 [/SUP], Christian Meyer Zu Natrup[SUP] 3 [/SUP], Tamara Tuchel[SUP] 1 [/SUP], Alina Tscherne[SUP] 4 [/SUP], Leonard Limpinsel[SUP] 4 [/SUP], Gerd Sutter[SUP] 4 [/SUP], Asisa Volz[SUP] 2 3 [/SUP], Wolfgang Baumgärtner[SUP] 1 2 [/SUP], Kirsten Hülskötter[SUP] #[/SUP][SUP] 1 [/SUP], Katharina Manuela Gregor[SUP] #[/SUP][SUP] 1 2 [/SUP]


Affiliations
Abstract

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.

Keywords: COVID-19; K18-hACE2 mice; SARS-CoV-2; modified vaccinia ankara-based vaccines; vaccines.

 
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