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

Chiuppesi, Flavia; Salazar, Marcela d’Alincourt; Contreras, Heidi; Nguyen, Vu H.; Martinez, Joy; Park, Yoonsuh; Nguyen, Jenny; Kha, Mindy; Iniguez, Angelina; Zhou, Qiao; Kaltcheva, Teodora; Levytskyy, Roman; Ebelt, Nancy D.; Kang, Tae Hyuk; Wu, Xiwei; Rogers, Thomas F.; 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 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.