Production and purification of chimeric HBc virus-like particles carrying influenza virus LAH domain as vaccine candidates

Andris Kazaks*, I. Na Lu, Sophie Farinelle, Alex Ramirez, Vincenzo Crescente, Benjamin Blaha, Olotu Ogonah, Tarit Mukhopadhyay, Mapi Perez de Obanos, Alejandro Krimer, Inara Akopjana, Janis Bogans, Velta Ose, Anna Kirsteina, Tatjana Kazaka, Nicola J. Stonehouse, David J. Rowlands, Claude P. Muller, Kaspars Tars, William M. Rosenberg

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

Background: The lack of a universal influenza vaccine is a global health problem. Interest is now focused on structurally conserved protein domains capable of eliciting protection against a broad range of influenza virus strains. The long alpha helix (LAH) is an attractive vaccine component since it is one of the most conserved influenza hemagglutinin (HA) stalk regions. For an improved immune response, the LAH domain from H3N2 strain has been incorporated into virus-like particles (VLPs) derived from hepatitis B virus core protein (HBc) using recently developed tandem core technology. Results: Fermentation conditions for recombinant HBc-LAH were established in yeast Pichia pastoris and a rapid and efficient purification method for chimeric VLPs was developed to match the requirements for industrial scale-up. Purified VLPs induced strong antibody responses against both group 1 and group 2 HA proteins in mice. Conclusion: Our results indicate that the tandem core technology is a useful tool for incorporation of highly hydrophobic LAH domain into HBc VLPs. Chimeric VLPs can be successfully produced in bioreactor using yeast expression system. Immunologic data indicate that HBc VLPs carrying the LAH antigen represent a promising universal influenza vaccine component.

Original languageEnglish
Article number79
JournalBMC Biotechnology
Volume17
Issue number1
DOIs
Publication statusPublished - 10 Nov 2017

Keywords

  • Influenza vaccine
  • Long alpha helix
  • Tandem-core
  • Virus-like particles
  • Yeast

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