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Updated: Mar 27, 2026
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Immunization with MVA-based vaccines protects K18-hACE2 mice from SARS-CoV-2 infection-associated inflammatory
Małgorzata Rosiak1,2, Sabrina Clever3, Eva Leitzen1
1Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
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.
Insights
Modified Vaccinia Virus Ankara (MVA) vaccines expressing SARS-CoV-2 spike protein prevent neuroinvasion and brain inflammation in mice. Vaccines with only nucleocapsid protein did not offer protection against neuroinflammation.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, with extrapulmonary effects including neurological complications.
- Understanding neuroprotective strategies against SARS-CoV-2 is crucial for mitigating long-term sequelae.
Purpose of the Study:
- To evaluate the neuroprotective potential of modified Vaccinia Virus Ankara (MVA)-based vaccines against SARS-CoV-2-induced neuroinflammation and neuroinvasion.
- To compare the efficacy of vaccines encoding different SARS-CoV-2 antigens (spike, nucleocapsid, or both) and assess various immunization timings.
Main Methods:
- K18-hACE2 mice were immunized with MVA vectors expressing SARS-CoV-2 spike (S), stabilized spike (ST), nucleocapsid (N), or ST+N proteins, alongside control groups (PBS, vector).
- Immunization protocols included prime-boost (twice) and single-dose regimens with infection at 2 days (emergency) or 4 weeks (prime) post-vaccination.
- Histopathological analysis of brains and retinas assessed inflammation (meningoencephalitis, microgliosis) and viral antigen presence in neurons.
Main Results:
- MVA vaccines encoding SARS-CoV-2 spike protein (S or ST) administered four weeks prior to infection completely prevented neuroinvasion and significantly reduced brain inflammation.
- Vaccines expressing only the nucleocapsid (N) protein, or control groups, exhibited mild to moderate meningoencephalitis, microgliosis, and widespread viral antigen in neurons.
- Single immunization before infection resulted in milder neuropathology compared to unvaccinated controls, with spike-protein-based vaccines showing the best protection.
Conclusions:
- MVA-based vaccines expressing SARS-CoV-2 spike protein confer significant neuroprotection against viral neuroinvasion and inflammation.
- Vaccine efficacy is dependent on the encoded antigen, with spike protein being critical for preventing neurological complications.
- Spike-protein-based MVA vaccination represents a promising strategy to mitigate the neurological impact of SARS-CoV-2 infection.
