Nat Commun
. 2020 Nov 30;11(1):6121.
doi: 10.1038/s41467-020-19819-1.
Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform
Flavia Chiuppesi 1 , Marcela d'Alincourt Salazar 1 , Heidi Contreras 1 , Vu H Nguyen 1 , Joy Martinez 1 , Yoonsuh Park 1 , Jenny Nguyen 1 , Mindy Kha 1 , Angelina Iniguez 1 , Qiao Zhou 1 , Teodora Kaltcheva 1 , Roman Levytskyy 1 , Nancy D Ebelt 2 , Tae Hyuk Kang 3 , Xiwei Wu 3 , Thomas F Rogers 4 5 , Edwin R Manuel 2 , Yuriy Shostak 6 , Don J Diamond 7 , Felix Wussow 8
Affiliations
- PMID: 33257686
- DOI: 10.1038/s41467-020-19819-1
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.