Immunogenicity of a DNA vaccine candidate for COVID-19

Trevor R.F. Smith, Ami Patel, Stephanie Ramos, Dustin Elwood, Xizhou Zhu, Jian Yan, Ebony N. Gary, Susanne N. Walker, Katherine Schultheis, Mansi Purwar, Ziyang Xu, Jewell Walters, Pratik Bhojnagarwala, Maria Yang, Neethu Chokkalingam, Patrick Pezzoli, Elizabeth Parzych, Emma L. Reuschel, Arthur Doan, Nicholas TursiMiguel Vasquez, Jihae Choi, Edgar Tello-Ruiz, Igor Maricic, Mamadou A. Bah, Yuanhan Wu, Dinah Amante, Daniel H. Park, Yaya Dia, Ali Raza Ali, Faraz I. Zaidi, Alison Generotti, Kevin Y. Kim, Timothy A. Herring, Sophia Reeder, Viviane M. Andrade, Karen Buttigieg, Gan Zhao, Jiun Ming Wu, Dan Li, Linlin Bao, Jiangning Liu, Wei Deng, Chuan Qin, Ami Shah Brown, Makan Khoshnejad, Nianshuang Wang, Jacqueline Chu, Daniel Wrapp, Jason S. McLellan, Kar Muthumani, Bin Wang, Miles W. Carroll, J. Joseph Kim, Jean Boyer, Daniel W. Kulp, Laurent M.P.F. Humeau, David B. Weiner, Kate E. Broderick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

231 Citations (Scopus)

Abstract

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.

Original languageEnglish
Article number2601
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020

Bibliographical note

Funding Information:
The studies described in this manuscript were funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI). The authors would like to additional thank Stacy Guzman at The Wistar Institute, and Olivia Bedoya, Gloria Mendez, Francisco Vega Vega and Jon Schantz at Inovio Pharmaceuticals for their assistance.

Publisher Copyright:
© 2020, The Author(s).

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