tetano
Editor, Senior Moderator
Vaccines (Basel)
. 2022 Jan 20;10(2):148.
doi: 10.3390/vaccines10020148.
The Highly Productive Thermothelomyces heterothallica C1 Expression System as a Host for Rapid Development of Influenza Vaccines
Gabor Keresztes[SUP] 1 [/SUP], Mark Baer[SUP] 2 [/SUP], Mark R Alfenito[SUP] 2 [/SUP], Theo C Verwoerd[SUP] 1 [/SUP], Andriy Kovalchuk[SUP] 3 [/SUP], Marilyn G Wiebe[SUP] 3 [/SUP], Tor Kristian Andersen[SUP] 4 [/SUP], Markku Saloheimo[SUP] 3 [/SUP], Ronen Tchelet[SUP] 1 [/SUP], Richard Kensinger[SUP] 5 [/SUP], Gunnveig Grødeland[SUP] 4 6 [/SUP], Mark Emalfarb[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Thermothelomyces heterothallica C1; filamentous fungi; influenza vaccine; recombinant protein expression; targeted influenza hemagglutinin; trimeric influenza hemagglutinin.
. 2022 Jan 20;10(2):148.
doi: 10.3390/vaccines10020148.
The Highly Productive Thermothelomyces heterothallica C1 Expression System as a Host for Rapid Development of Influenza Vaccines
Gabor Keresztes[SUP] 1 [/SUP], Mark Baer[SUP] 2 [/SUP], Mark R Alfenito[SUP] 2 [/SUP], Theo C Verwoerd[SUP] 1 [/SUP], Andriy Kovalchuk[SUP] 3 [/SUP], Marilyn G Wiebe[SUP] 3 [/SUP], Tor Kristian Andersen[SUP] 4 [/SUP], Markku Saloheimo[SUP] 3 [/SUP], Ronen Tchelet[SUP] 1 [/SUP], Richard Kensinger[SUP] 5 [/SUP], Gunnveig Grødeland[SUP] 4 6 [/SUP], Mark Emalfarb[SUP] 1 [/SUP]
Affiliations
- PMID: 35214607
- PMCID: PMC8877961
- DOI: 10.3390/vaccines10020148
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.
Keywords: Thermothelomyces heterothallica C1; filamentous fungi; influenza vaccine; recombinant protein expression; targeted influenza hemagglutinin; trimeric influenza hemagglutinin.