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