Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform
Flavia Chiuppesi, Marcela D Salazar, Heidi Contreras, Vu H. Nguyen, Joy Martinez, Yoonsuh Park, Jenny Nguyen, Mindy Kha, Angelina Iniguez, Qiao Zhou, Teodora Kaltcheva, Roman M. Levytskyy, Nancy D. Ebelt, Tae Hyuk Kang, Xiwei Wu, Thomas F. Rogers, Edwin R. Manuel, Yuriy Shostak, Don J. Diamond, Felix Wussow
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.