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

Author:

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 JORCID,Wussow Felix

Abstract

AbstractModified 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.

Publisher

Cold Spring Harbor Laboratory

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