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

Author:

Chiuppesi FlaviaORCID,Salazar Marcela d’Alincourt,Contreras Heidi,Nguyen Vu H.,Martinez Joy,Park Yoonsuh,Nguyen Jenny,Kha Mindy,Iniguez Angelina,Zhou Qiao,Kaltcheva Teodora,Levytskyy RomanORCID,Ebelt Nancy D.ORCID,Kang Tae HyukORCID,Wu Xiwei,Rogers Thomas F.,Manuel Edwin R.,Shostak YuriyORCID,Diamond Don J.ORCID,Wussow FelixORCID

Abstract

AbstractModified 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

City of Hope PDDV Program COH04

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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