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

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

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.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and, as of October 27, 2021, had infected over 244 million people and caused over 4.8 million deaths
With new variants of concern starting to dominate the human pandemic, new derivatives of the current vaccines may be necessary for continued protection from SARS-CoV-2 infection
We have developed a vaccine that uses a safe vesicular stomatitis virus-based delivery vehicle to present a key SARS-CoV-2 protein to our immune system in order to train it to recognize and prevent SARS-CoV-2 infection

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and, as of October 27, 2021, had infected over 244 million people and caused over 4.8 million deaths. The global pandemic has resulted in massive societal and economic disruption worldwide [1]. SARS-CoV-2 belongs to the Betacoronavirus genus which includes recently emerged human pathogenic coronaviruses SARS-CoV and MERS-CoV. SARS-CoV-2 primarily targets the lungs in humans. It targets other organs such as the heart, liver and kidneys. SARS-CoV-2 infection can lead to multiple organ failure, shock, acute respiratory distress syndrome, heart failure, arrhythmias, and renal failure [2,3]

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