A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2

Alena Reguzova; Melanie Müller; Felix Pagallies; Dominique Burri; Ferdinand Salomon; Hanns Joachim Rziha; Zsofia Bittner-Schrader; Babs E. Verstrepen; Kinga P. Böszörményi; Ernst J. Verschoor; Ingo Gerhauser; Knut Elbers; Meral Esen; Alessandro Manenti; Martina Monti; Hans Georg Rammensee; Madiha Derouazi; Markus W. Löffler; Ralf Amann

doi:10.1038/s41541-024-00981-2

A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2

Alena Reguzova
, Melanie Müller
, Felix Pagallies
, Dominique Burri
, Ferdinand Salomon
, Hanns Joachim Rziha
, Zsofia Bittner-Schrader
, Babs E. Verstrepen
, Kinga P. Böszörményi
, Ernst J. Verschoor
, Ingo Gerhauser
, Knut Elbers
, Meral Esen
, Alessandro Manenti
, Martina Monti
, Hans Georg Rammensee
, Madiha Derouazi
, Markus W. Löffler^*
, Ralf Amann^*

^*Corresponding author for this work

Virology

University Hospital Tübingen
Speransa Therapeutics
Biomedical Primate Research Centre
University of Veterinary Medicine Hannover, Foundation
Boehringer Ingelheim GmbH
ViraTherapeutics GmbH
University of Tübingen
German Center for Infection Research; partner site Tübingen
VisMederi S.r.l.
Centre for Clinical Transfusion Medicine Tuebingen (ZKT)

Research output: Contribution to journal › Article › Academic › peer-review

7 Citations (Scopus)

24 Downloads (Pure)

Abstract

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.

Original language	English
Article number	191
Journal	npj Vaccines
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41541-024-00981-2
Publication status	Published - 16 Oct 2024

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Publisher Copyright:
© The Author(s) 2024.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2Final published version, 2.36 MBLicence: CC BY

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Reguzova, A., Müller, M., Pagallies, F., Burri, D., Salomon, F., Rziha, H. J., Bittner-Schrader, Z., Verstrepen, B. E., Böszörményi, K. P., Verschoor, E. J., Gerhauser, I., Elbers, K., Esen, M., Manenti, A., Monti, M., Rammensee, H. G., Derouazi, M., Löffler, M. W., & Amann, R. (2024). A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2. npj Vaccines, 9(1), Article 191. https://doi.org/10.1038/s41541-024-00981-2

@article{5a81ed304bdb42598cd460c643d9646e,

title = "A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2",

abstract = "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.",

author = "Alena Reguzova and Melanie M{\"u}ller and Felix Pagallies and Dominique Burri and Ferdinand Salomon and Rziha, \{Hanns Joachim\} and Zsofia Bittner-Schrader and Verstrepen, \{Babs E.\} and B{\"o}sz{\"o}rm{\'e}nyi, \{Kinga P.\} and Verschoor, \{Ernst J.\} and Ingo Gerhauser and Knut Elbers and Meral Esen and Alessandro Manenti and Martina Monti and Rammensee, \{Hans Georg\} and Madiha Derouazi and L{\"o}ffler, \{Markus W.\} and Ralf Amann",

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year = "2024",

month = oct,

day = "16",

doi = "10.1038/s41541-024-00981-2",

language = "English",

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Reguzova, A, Müller, M, Pagallies, F, Burri, D, Salomon, F, Rziha, HJ, Bittner-Schrader, Z, Verstrepen, BE, Böszörményi, KP, Verschoor, EJ, Gerhauser, I, Elbers, K, Esen, M, Manenti, A, Monti, M, Rammensee, HG, Derouazi, M, Löffler, MW & Amann, R 2024, 'A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2', npj Vaccines, vol. 9, no. 1, 191. https://doi.org/10.1038/s41541-024-00981-2

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

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 - https://www.scopus.com/pages/publications/85206700326

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 -

A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2

Abstract

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