Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Vaccinia Virus Strain Mva Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

María M Lorenzo
,
Alejandro Marín-López
,
Kevin Chiem
,
Luis Jimenez-Cabello
ORCID logo ,
Irfan Ullah
,
Sergio Utrilla-Trigo
,
Eva Calvo-Pinilla
ORCID logo ,
Gema Lorenzo
,
Sandra Moreno
ORCID logo ,
Chengjin Ye
,
Jun-Gyu Park
,
Alejandro Matía
,
Alejandro Brun
,
Juana M Sánchez-Puig
,
Aitor Nogales
,
Walther Mothes
,
Pradeep D Uchil
ORCID logo ,
Priti Kumar
,
Javier Ortego
,
Erol Fikrig
,
Luis Martinez-Sobrido
* ,
Rafael Blasco
*
Version 1 : Received: 3 May 2023 / Approved: 4 May 2023 / Online: 4 May 2023 (07:48:34 CEST)

A peer-reviewed article of this Preprint also exists.

Lorenzo, M.M.; Marín-López, A.; Chiem, K.; Jimenez-Cabello, L.; Ullah, I.; Utrilla-Trigo, S.; Calvo-Pinilla, E.; Lorenzo, G.; Moreno, S.; Ye, C.; Park, J.-G.; Matía, A.; Brun, A.; Sánchez-Puig, J.M.; Nogales, A.; Mothes, W.; Uchil, P.D.; Kumar, P.; Ortego, J.; Fikrig, E.; Martinez-Sobrido, L.; Blasco, R. Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models. Vaccines 2023, 11, 1006. Lorenzo, M.M.; Marín-López, A.; Chiem, K.; Jimenez-Cabello, L.; Ullah, I.; Utrilla-Trigo, S.; Calvo-Pinilla, E.; Lorenzo, G.; Moreno, S.; Ye, C.; Park, J.-G.; Matía, A.; Brun, A.; Sánchez-Puig, J.M.; Nogales, A.; Mothes, W.; Uchil, P.D.; Kumar, P.; Ortego, J.; Fikrig, E.; Martinez-Sobrido, L.; Blasco, R. Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models. Vaccines 2023, 11, 1006.

Abstract

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

Keywords

Poxvirus; Modified Vaccinia virus Ankara; vaccine; SARS-CoV-2; COVID-19; recombinant viral vectors; immunization

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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