Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle.

Joshua M Royal,Gregory P Pogue,Carrie A Simpson,Thomas W Geisbert,John Shepherd,Steve Hume,Hugh Haydon,Viktoriya Borisevich,Richard J Webby,Amanda Phillips,Robert W Cross,Kelsi Swope,Youngjun Oh,Jennifer K Demarco,Barry Bratcher,Alison A Mccormick,Josh Morton,Jennifer L Debeauchamp

doi:10.3390/vaccines9111347

Abstract

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.

Highlights

To date, seven coronaviruses (CoVs) capable of infecting humans have been identified, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the newly identified CoV, SARS-CoV-2 [1]
By identifying the dilution of pooled sera that reduced 50% of plaques of SARS-CoV-2 virus in VeroE6 cells (PRNT50), we found that non-adjuvanted CoV-RBD121-NP at the 45 μg dose produced the highest value (Figure 5A, left)
The COVID-19 pandemic has spurred the development of vaccine candidates utilizing a wide range of vaccine platforms [5]

Summary

Introduction

Seven coronaviruses (CoVs) capable of infecting humans have been identified, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the newly identified CoV, SARS-CoV-2 [1]. Infection with any of these three viruses is associated with high morbidity and fatality rates [2]. As of 13 June 2021, this virus has infected >175 million people and has been attributed to >3.5 million deaths worldwide [3]. The COVID-19 pandemic created worldwide health and economic crises. The number of new daily reported cases has been declining since May 2021, daily global deaths attributed to COVID-19 continue to oscillate. The emergence of new variants presents ongoing challenges to controlling the pandemic and an urgent need for the development of new vaccine platforms with the ability to adapt to new viral strains as they develop

Methods

Results

Conclusion