Optimized vaccine candidate MVA-S(3P) fully protects against SARS-CoV-2 infection in hamsters

Front Immunol. 2023 Oct 18:14:1163159. doi: 10.3389/fimmu.2023.1163159. eCollection 2023.

Abstract

The development of novel optimized vaccines against coronavirus disease 2019 (COVID-19) that are capable of controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the appearance of different variants of concern (VoC) is needed to fully prevent the transmission of the virus. In the present study, we describe the enhanced immunogenicity and efficacy elicited in hamsters by a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein [termed MVA-S(3P)]. Hamsters vaccinated with one or two doses of MVA-S(3P) developed high titers of S-binding IgG antibodies and neutralizing antibodies against the ancestral Wuhan SARS-CoV-2 virus and VoC beta, gamma, and delta, as well as against omicron, although with a somewhat lower neutralization activity. After SARS-CoV-2 challenge, vaccinated hamsters did not lose body weight as compared to matched placebo (MVA-WT) controls. Consistently, vaccinated hamsters exhibited significantly reduced viral RNA in the lungs and nasal washes, and no infectious virus was detected in the lungs in comparison to controls. Furthermore, almost no lung histopathology was detected in MVA-S(3P)-vaccinated hamsters, which also showed significantly reduced levels of proinflammatory cytokines in the lungs compared to unvaccinated hamsters. These results reinforce the use of MVA-S(3P) as a vaccine candidate against COVID-19 in clinical trials.

Keywords: COVID-19; MVA-S(3P) vaccine candidate; SARS-CoV-2; efficacy; hamsters; immunogenicity; prefusion-stabilized spike; variants of concern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • COVID-19* / prevention & control
  • Cricetinae
  • SARS-CoV-2
  • Vaccinia virus / genetics

Substances

  • Antibodies, Neutralizing

Supplementary concepts

  • Modified Vaccinia Ankara virus

Grants and funding

The authors declare that this study received funding from Fondo COVID-19 grant COV20/00151 (Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)), Fondo Supera COVID-19 grant (Crue Universidades-Banco Santander), Spanish Research Council (CSIC) grant 202120E079, and funds from Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC) co-financed with FEDER funds (to JG-A), CSIC grant 2020E84, La CaixaImpulse grant CF01-00008, Ferrovial and MAPFRE donations (to ME), a Spanish Ministry of Science and Innovation (MCIN)/Spanish Research Agency (AEI)/10.13039/501100011033 grant (PID2020-114481RB-I00 to JG-A and ME), and internal funding from KU Leuven (to JN) and the Flemish Research Foundation (FWO) Excellence of Science (EOS) program (No. 40007527; VirEOS2) (to KD and JN). This research work was also funded by the European Commission-Next Generation EU through CSIC’s Global Health Platform (PTI Salud Global) (to JG-A and ME). JG-A and ME also acknowledge financial support from the Spanish State Research Agency, AEI/10.13039/501100011033, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2013-0347, SEV-2017-0712). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.