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

Flavia Chiuppesi(City Of Hope National Medical Center), Marcela D 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 M. Levytskyy(City Of Hope National Medical Center), Nancy D. Ebelt(City of Hope), Tae Hyuk Kang(City of Hope), Xiwei Wu(City of Hope), Thomas F. Rogers(Scripps Institution of Oceanography), Edwin R. Manuel(City of Hope), Yuriy Shostak(City of Hope), Don J. Diamond(City Of Hope National Medical Center), Felix Wussow(City Of Hope National Medical Center)
Nature Communications
November 30, 2020
10.1038/s41467-020-19819-1
Cited by 104Open Access
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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.

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