A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2
Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine.
Authors
- Ernst J. Verschoor (ORCID: https://orcid.org/0000-0003-0912-2074)
- Ingo Gerhauser (ORCID: https://orcid.org/0000-0002-7973-7405)
- Madiha Derouazi (ORCID: https://orcid.org/0000-0001-9412-9558)
- Ferdinand Salomon
- Markus Löffler (ORCID: https://orcid.org/0000-0003-2513-1317)
- Felix Pagallies (ORCID: https://orcid.org/0000-0002-1307-192X)
- Alena Reguzova
- Ralf Amann (ORCID: https://orcid.org/0009-0005-8482-2240)
- Martina Monti (ORCID: https://orcid.org/0000-0002-2173-7269)
- Babs E. Verstrepen (ORCID: https://orcid.org/0000-0002-4666-0798)
- Knut Elbers
- Alessandro Manenti (ORCID: https://orcid.org/0000-0002-4027-7296)
- Kinga P. Böszörményi (ORCID: https://orcid.org/0000-0001-5330-2617)
- Dominique J. Burri
- Hans‐Georg Rammensee (ORCID: https://orcid.org/0000-0003-1614-2647)
- Zsofia Bittner-Schrader
- Melanie Müller (ORCID: https://orcid.org/0000-0002-5845-7738)
- Meral Esen
- Hanns-Joachim Rziha
Institutions
- Boehringer Ingelheim (Germany) (DE)
- University of Veterinary Medicine Hannover, Foundation (DE)
- Erasmus MC (NL)
- Biomedical Primate Research Centre (NL)
- Cardiovascular Center Bethanien (DE)
- Vienna Consulting Engineers (Austria) (AT)
- German Center for Infection Research (DE)
- VisMederi Research (IT)
- University of Tübingen (DE)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-10-16
- DOI
- https://doi.org/10.1038/s41541-024-00981-2
- Citations
- 7
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.72
Funders
- Carl-Zeiss-Stiftung
- Eberhard Karls Universität Tübingen