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


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.

SUBMITTER: Gonzalez-Hernandez M 

PROVIDER: S-EPMC10289020 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

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

Gonzalez-Hernandez Mariana M   Kaiser Franziska Karola FK   Steffen Imke I   Ciurkiewicz Malgorzata M   van Amerongen Geert G   Tchelet Ronen R   Emalfarb Mark M   Saloheimo Markku M   Wiebe Marilyn G MG   Vitikainen Marika M   Albulescu Irina C IC   Bosch Berend-Jan BJ   Baumgärtner Wolfgang W   Haagmans Bart L BL   Osterhaus Albert D M E ADME  

Frontiers in immunology 20230609


<h4>Introduction</h4>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.<h4>Methods</h4>A SARS-CoV-2 RBD vaccine candidate was produced in the  ...[more]

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