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

• Published in: Frontiers in Immunology
• Main Authors: Mariana Gonzalez-Hernandez, Franziska Karola Kaiser, Imke Steffen, Malgorzata Ciurkiewicz, Geert van Amerongen, Ronen Tchelet, Mark Emalfarb, Markku Saloheimo, Marilyn G. Wiebe, Marika Vitikainen, Irina C. Albulescu, Berend-Jan Bosch, Wolfgang Baumgärtner, Bart L. Haagmans, Albert D. M. E. Osterhaus
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2023-06-01
• Subjects: SARS-CoV-2; receptor-binding domain; vaccine; hamster; Thermothelomyces heterothallica; C1
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1204834/full
• ISSN: 1664-3224

IntroductionThe 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.MethodsA 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.ResultsOne 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.DiscussionOur 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.