Production and purification of chimeric HBc virus-like particles carrying influenza virus LAH domain as vaccine candidates
Authors/Creators
-
Kazaks, Andris1
- Lu, I-Na2
- Farinelle, Sophie2
- Ramirez, Alex3
- Crescente, Vincenzo3
- Blaha, Benjamin4
- Ogonah, Olotu4
- Mukhopadhyay, Tarit4
- de Obanos, Mapi Perez5
- Krimer, Alejandro5
- Akopjana, Inara1
- Bogans, Janis1
- Ose, Velta1
- Kirsteina, Anna1
- Kazaka, Tatjana1
- Stonehouse, Nicola J.6
- Rowlands, David J.6
- Muller, Claude P.2
- Tars, Kaspars1
- Rosenberg, William M.3
- 1. Latvian Biomedical Research and Study Centre, Ratsupites 1, Riga, LV-1067, Latvia
- 2. Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg
- 3. iQur Limited, 2 Royal College Street, London, NW1 0NH, UK
- 4. Department of Biochemical Engineering, University College London, Gower Street, London, WC1E 6BT, UK
- 5. 3P Biopharmaceuticals SL, Calle Mocholi 2 Poligono Mocholi, Noain, 31110, Navarra, Spain
- 6. Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK
Description
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.