Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

Chiuppesi, Flavia; Salazar, Marcela d’Alincourt; Contreras, Heidi; Nguyen, Vu H; Martinez, Joy; Park, Soojin; Nguyen, Jenny; Kha, Mindy; Iniguez, Angelina; Zhou, Qiao; Kaltcheva, Teodora; Levytskyy, Roman; Ebelt, Nancy D; Kang, Tae Hyuk; Wu, Xiwei; Rogers, Thomas; Manuel, Edwin R; Shostak, Yuriy; Diamond, Don J; Wussow, Felix

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel 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 used this novel 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. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel 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.