Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD-based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica C1

Front Immunol. 2023 Jun 9:14:1204834. doi: 10.3389/fimmu.2023.1204834. eCollection 2023.

Abstract

Introduction: The emergency use of vaccines has been the most efficient way to control the coronavirus disease 19 (COVID-19) pandemic. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is the main target for virus neutralizing (VN) antibodies.

Methods: A SARS-CoV-2 RBD vaccine candidate was produced in the Thermothelomyces heterothallica (formerly, Myceliophthora thermophila) C1 protein expression system and coupled to a nanoparticle. Immunogenicity and efficacy of this vaccine candidate was tested using the Syrian golden hamster (Mesocricetus auratus) infection model.

Results: One dose of 10-μg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies neutralized SARS-CoV-2 variants of concern: D614G, Alpha, Beta, Gamma, and Delta.

Discussion: Our results support the use of the Thermothelomyces heterothallica C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections to help overcome limitations associated with the use of mammalian expression system.

Keywords: C1; SARS-CoV-2; Thermothelomyces heterothallica; filamentous fungus; hamster; receptor-binding domain; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Blocking
  • COVID-19 Vaccines*
  • COVID-19* / prevention & control
  • Cricetinae
  • Fungi
  • Humans
  • Mesocricetus
  • SARS-CoV-2 / genetics

Substances

  • COVID-19 Vaccines
  • Adjuvants, Immunologic
  • Antibodies, Blocking

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was performed as part of the Zoonotic Anticipation and Preparedness Initiative (ZAPI project) [Innovative Medicines initiative (IMI) grant 115760], with assistance and financial support from IMI and the European Commission and contributions from EFPIA partners. BH is supported by the NIH/NIAID Centers of Excellence for Influenza Research and Response (CEIRR) under contract 75N93021C00014, Icahn School of Medicine at Mt. Sinai. This research was also funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation, 398066876/GRK 2485/1, to AO, FK, IS, and WB), by the Ministry of Science and Culture of Lower Saxony in Germany (14 – 76103–184 CORONA-15/20, to WB and AO), and by the COVID-19 Research Network of the State of Lower Saxony (COFONI) with funding from the ministry of science and culture of Lower Saxony, Germany (14–76403–184, to FA, MC, and WB).This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491094227 “Open Access Publication Costs” and the University of Veterinary Medicine Hannover Foundation. IA was funded through the Utrecht Molecular Immunology Hub (Utrecht University).