TY - JOUR
T1 - A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2
AU - Reguzova, Alena
AU - Müller, Melanie
AU - Pagallies, Felix
AU - Burri, Dominique
AU - Salomon, Ferdinand
AU - Rziha, Hanns Joachim
AU - Bittner-Schrader, Zsofia
AU - Verstrepen, Babs E.
AU - Böszörményi, Kinga P.
AU - Verschoor, Ernst J.
AU - Gerhauser, Ingo
AU - Elbers, Knut
AU - Esen, Meral
AU - Manenti, Alessandro
AU - Monti, Martina
AU - Rammensee, Hans Georg
AU - Derouazi, Madiha
AU - Löffler, Markus W.
AU - Amann, Ralf
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/10/16
Y1 - 2024/10/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85206700326&partnerID=8YFLogxK
U2 - 10.1038/s41541-024-00981-2
DO - 10.1038/s41541-024-00981-2
M3 - Article
C2 - 39414789
AN - SCOPUS:85206700326
SN - 2059-0105
VL - 9
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 191
ER -