Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

Flavia Chiuppesi, Marcela d’Alincourt Salazar, Heidi Contreras, Vu H. Nguyen, Joy Martinez, Yoonsuh Park, Jenny Nguyen, Mindy Kha, Angelina Iniguez, Qiao Zhou, Teodora Kaltcheva, Roman Levytskyy, Nancy D. Ebelt, Tae Hyuk Kang, Xiwei Wu, Thomas F. Rogers, Edwin R. Manuel, Yuriy Shostak, Don J. Diamond () and Felix Wussow ()
Additional contact information
Flavia Chiuppesi: City of Hope National Medical Center
Marcela d’Alincourt Salazar: City of Hope National Medical Center
Heidi Contreras: City of Hope National Medical Center
Vu H. Nguyen: City of Hope National Medical Center
Joy Martinez: City of Hope National Medical Center
Yoonsuh Park: City of Hope National Medical Center
Jenny Nguyen: City of Hope National Medical Center
Mindy Kha: City of Hope National Medical Center
Angelina Iniguez: City of Hope National Medical Center
Qiao Zhou: City of Hope National Medical Center
Teodora Kaltcheva: City of Hope National Medical Center
Roman Levytskyy: City of Hope National Medical Center
Nancy D. Ebelt: Beckman Research Institute of the City of Hope
Tae Hyuk Kang: Integrative Genomics Core, Beckman Research Institute of the City of Hope
Xiwei Wu: Integrative Genomics Core, Beckman Research Institute of the City of Hope
Thomas F. Rogers: University of California San Diego, School of Medicine
Edwin R. Manuel: Beckman Research Institute of the City of Hope
Yuriy Shostak: Research Business Development, City of Hope
Don J. Diamond: City of Hope National Medical Center
Felix Wussow: City of Hope National Medical Center

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

Date: 2020
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DOI: 10.1038/s41467-020-19819-1

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