Journal Article

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

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

2021

Overview

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 (S F ), 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-S F -Gtc proved to be the superior immunogen. More importantly, rVSV-msp-S F -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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenoviruses / Amino acids / Angiotensin-Converting Enzyme 2 - genetics / Angiotensin-Converting Enzyme 2 - metabolism / Animals / Antibodies / Antibodies, Neutralizing - immunology / Antibodies, Viral - immunology / Antigens / Bees / Biology and life sciences / Chimeras / Chlorocebus aethiops / Clinical trials / Coronaviruses / COVID-19 / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 - virology / COVID-19 vaccines / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - genetics / DNA vaccines / Ebola virus / Genes / Genetic aspects / Genetic vectors / Genomes / Glycoproteins / Health aspects / Humans / Immune response / Immunization / Immunological research / Lungs / Lymphocytes / Lymphocytes T / Medicine and health sciences / Mice / Mice, Inbred C57BL / Mice, Transgenic / Middle East respiratory syndrome / mRNA vaccines / Mutation / N-Terminus / Neutralizing / Pandemics / Peptides / Protein expression / Proteins / Research and Analysis Methods / Rhabdoviruses / RNA polymerase / SARS-CoV-2 - immunology / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Spike Glycoprotein, Coronavirus - metabolism / Spike protein / Stomatitis / Vaccines / Vectors (Biology) / Vero Cells / Vesicular stomatitis Indiana virus - genetics / Viral Proteins - genetics / Viral Proteins - immunology / Viruses