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PLoS Pathog. 2021 Dec 16;17(12):e1010092. doi: 10.1371/journal.ppat.1010092. eCollection 2021 Dec.

A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

PLoS pathogens

Gyoung Nyoun Kim, Jung-Ah Choi, Kunyu Wu, Nasrin Saeedian, Eunji Yang, Hayan Park, Sun-Je Woo, Gippeum Lim, Seong-Gyu Kim, Su-Kyeong Eo, Hoe Won Jeong, Taewoo Kim, Jae-Hyung Chang, Sang Hwan Seo, Na Hyung Kim, Eunsil Choi, Seungho Choo, Sangkyun Lee, Andrew Winterborn, Yue Li, Kate Parham, Justin M Donovan, Brock Fenton, Jimmy D Dikeakos, Gregory A Dekaban, S M Mansour Haeryfar, Ryan M Troyer, Eric J Arts, Stephen D Barr, Manki Song, C Yong Kang

Affiliations

  1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
  2. International Vaccine Institute, SNU Research Park, 1 Gwanak-ro, Gwanak-gu, Seoul, Korea.
  3. Sumagen, 4F Dongwon Bldg, Teheran-ro 77-gil, Gangnam-gu, Seoul, Korea.
  4. Animal Facility, Queen's University, Kinston, Ontario, Canada.
  5. Department of Biology, Faculty of Science, The University of Western Ontario, London, Ontario, Canada.
  6. Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

PMID: 34914812 PMCID: PMC8675757 DOI: 10.1371/journal.ppat.1010092

Abstract

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (SF), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-SF-Gtc proved to be the superior immunogen. More importantly, rVSV-msp-SF-Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

Conflict of interest statement

The authors have declared that no competing interests exist.

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