Frontiers in Virology (May 2022)

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

  • Moonsup Jeong,
  • Sagar B. Kudchodkar,
  • Areum Gil,
  • Bohyun Jeon,
  • Gee Ho Park,
  • Youngran Cho,
  • Hyojin Lee,
  • Mi Sun Cheong,
  • Wonil Kim,
  • Yun-Ho Hwang,
  • Jung-Ah Lee,
  • Heeji Lim,
  • Mi Young Kim,
  • Emran O. Lallow,
  • Tej Brahmbhatt,
  • Stephen A. Kania,
  • Nandita C. Jhumur,
  • Jerry W. Shan,
  • Jeffrey D. Zahn,
  • David I. Shreiber,
  • Jonathan P. Singer,
  • Hao Lin,
  • Erin K. Spiegel,
  • Laurent Pessaint,
  • Maciel Porto,
  • Alex Van Ry,
  • Danielle Nase,
  • Swagata Kar,
  • Hanne Andersen,
  • Ian Tietjen,
  • Joel Cassel,
  • Joseph M. Salvino,
  • Luis J. Montaner,
  • Young K. Park,
  • Kar Muthumani,
  • Christine C. Roberts,
  • Joel N. Maslow

DOI
https://doi.org/10.3389/fviro.2022.891540
Journal volume & issue
Vol. 2

Abstract

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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.

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