The Highly Productive Thermothelomyces heterothallica C1 Expression System as a Host for Rapid Development of Influenza Vaccines

Autor: Gabor Keresztes, Mark Baer, Mark R. Alfenito, Theo C. Verwoerd, Andriy Kovalchuk, Marilyn G. Wiebe, Tor Kristian Andersen, Markku Saloheimo, Ronen Tchelet, Richard Kensinger, Gunnveig Grødeland, Mark Emalfarb
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Vaccines, Vol 10, Iss 2, p 148 (2022)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines10020148
Popis: (1) Influenza viruses constantly change and evade prior immune responses, forcing seasonal re-vaccinations with updated vaccines. Current FDA-approved vaccine manufacturing technologies are too slow and/or expensive to quickly adapt to mid-season changes in the virus or to the emergence of pandemic strains. Therefore, cost-effective vaccine technologies that can quickly adapt to newly emerged strains are desirable. (2) The filamentous fungal host Thermothelomyces heterothallica C1 (C1, formerly Myceliophthora thermophila) offers a highly efficient and cost-effective alternative to reliably produce immunogens of vaccine quality at large scale. (3) We showed the utility of the C1 system expressing hemagglutinin (HA) and a HA fusion protein from different H1N1 influenza A virus strains. Mice vaccinated with the C1-derived HA proteins elicited anti-HA immune responses similar, or stronger than mice vaccinated with HA products derived from prototypical expression systems. A challenge study demonstrated that vaccinated mice were protected against the aggressive homologous viral challenge. (4) The C1 expression system is proposed as part of a set of protein expression systems for plug-and-play vaccine manufacturing platforms. Upon the emergence of pathogens of concern these platforms could serve as a quick solution for producing enough vaccines for immunizing the world population in a much shorter time and more affordably than is possible with current platforms.
Databáze: Directory of Open Access Journals