Immune Responses of a Novel Bi-Cistronic SARS-CoV-2 DNA Vaccine Following Intradermal Immunization With Suction Delivery

• Published in: Frontiers in virology (online) Vol. 2
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 24.05.2022
• Subjects: antibody; Bi-cistronic DNA vaccine; SARS-CoV-2; SARS-CoV-2 variant of concern; T cell; viral challenge
• ISSN: 2673-818X; 2673-818X
• DOI: 10.3389/fviro.2022.891540

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.