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 language | English |
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Article number | 148 |
Number of pages | 19 |
Journal | Vaccines |
Volume | 10 |
Issue number | 2 |
DOIs | |
Publication status | Published - 20 Jan 2022 |
MoE publication type | A1 Journal article-refereed |
Funding
The development of the Thermothelomyces. heterothallica C1 expression system received no external funding. The expression of full-length influenza hemagglutinin was conducted in collaboration with Sanofi Pasteur. Assessing the immunogenicity of C1-produced HA was covered by AFAPIS#16508-2018081313297024 v1, approved by the French ministry of research and innovation. The investigation of the immunogenicity of αMHCII was funded by innovation funds from UiO.
Keywords
- Filamentous fungi
- Influenza vaccine
- Recombinant protein expression
- Targeted influenza hemagglutinin
- Thermothelomyces heterothallica C1
- Trimeric influenza hemagglutinin