Journal Article

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

Gonzalez-Hernandez, Mariana, Steffen, Imke, Saloheimo, Markku, Osterhaus, Albert D. M. E., Wiebe, Marilyn G., Vitikainen, Marika, Albulescu, Irina C., Emalfarb, Mark, Baumgärtner, Wolfgang, Ciurkiewicz, Malgorzata, Tchelet, Ronen, Haagmans, Bart L., van Amerongen, Geert, Bosch, Berend-Jan, Kaiser, Franziska Karola

2023

Overview

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. 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. 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. 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adjuvants / Adjuvants, Immunologic / Aluminum hydroxide / Animals / Antibodies / Antibodies, Blocking / Bacteria / C1 protein / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 Vaccines / Cricetinae / Enzymes / Fungi / hamster / Humans / Immunization / Immunogenicity / Immunology / Mesocricetus / Mesocricetus auratus / Nanoparticles / Pandemics / Protein expression / Proteins / receptor-binding domain / SARS-CoV-2 / SARS-CoV-2 - genetics / Severe acute respiratory syndrome coronavirus 2 / Thermothelomyces heterothallica / vaccine / Vaccines