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

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 (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

(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.

Original languageEnglish
Article number148
Number of pages19
JournalVaccines
Volume10
Issue number2
DOIs
Publication statusPublished - 20 Jan 2022
MoE publication typeA1 Journal article-refereed

Keywords

  • Filamentous fungi
  • Influenza vaccine
  • Recombinant protein expression
  • Targeted influenza hemagglutinin
  • Thermothelomyces heterothallica C1
  • Trimeric influenza hemagglutinin

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