AUTHOR=Jeong Moonsup , Kudchodkar Sagar B. , Gil Areum , Jeon Bohyun , Park Gee Ho , Cho Youngran , Lee Hyojin , Cheong Mi Sun , Kim Wonil , Hwang Yun-Ho , Lee Jung-Ah , Lim Heeji , Kim Mi Young , Lallow Emran O. , Brahmbhatt Tej , Kania Stephen A. , Jhumur Nandita C. , Shan Jerry W. , Zahn Jeffrey D. , Shreiber David I. , Singer Jonathan P. , Lin Hao , Spiegel Erin K. , Pessaint Laurent , Porto Maciel , Van Ry Alex , Nase Danielle , Kar Swagata , Andersen Hanne , Tietjen Ian , Cassel Joel , Salvino Joseph M. , Montaner Luis J. , Park Young K. , Muthumani Kar , Roberts Christine C. , Maslow Joel N. TITLE=Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery JOURNAL=Frontiers in Virology VOLUME=2 YEAR=2022 URL=https://www.frontiersin.org/journals/virology/articles/10.3389/fviro.2022.891540 DOI=10.3389/fviro.2022.891540 ISSN=2673-818X ABSTRACT=

SARS-CoV-2 is the third pathogenic coronavirus to emerge since 2000. Experience from prior outbreaks of SARS-CoV and MERS-CoV has demonstrated the importance of both humoral and cellular immunity to clinical outcome, precepts that have been recapitulated for SARS-CoV-2. Despite the unprecedented rapid development and deployment of vaccines against SARS-CoV-2, more vaccines are needed to meet global demand and to guard against immune evasion by newly emerging SARS-CoV-2 variants. Here we describe the development of pGO-1002, a novel bi-cistronic synthetic DNA vaccine that encodes consensus sequences of two SARS-CoV-2 antigens, Spike and ORF3a. Mice immunized with pGO-1002 developed humoral and cellular responses to both antigens, including antibodies and capable of neutralizing infection by a clinical SARS-CoV-2 isolate. Rats immunized with pGO-1002 by intradermal (ID) injection followed by application of suction with our GeneDerm device also developed humoral responses that included neutralizing antibodies and RBD-ACE2 blocking antibodies as well as robust cellular responses to both antigens. Significantly, in a Syrian hamster vaccination and challenge model, ID+GeneDerm-assisted vaccination prevented viral replication in the lungs and significantly reduced viral replication in the nares of hamsters challenged with either an ancestral SARS-CoV-2 strain or the B.1.351 (Beta) variant of concern. Furthermore, vaccinated immune sera inhibited virus-mediated cytopathic effects in vitro. These data establish the immunogenicity of the SARS-CoV-2 vaccine candidate pGO-1002 which induces potent humoral and cellular responses to the Spike and ORF3a antigens and may provide greater protection against emerging variants.