1. Production and purification of chimeric HBc virus-like particles carrying influenza virus LAH domain as vaccine candidates
- Author
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Kaspars Tars, Tatjana Kazaka, Andris Kazaks, Benjamin A. F. Bláha, I-Na Lu, Mapi Perez de Obanos, Inara Akopjana, Anna Kirsteina, Tarit Mukhopadhyay, Sophie Farinelle, Velta Ose, Nicola J. Stonehouse, William Rosenberg, Alejandro Krimer, Olotu Ogonah, Alex Ramirez, Janis Bogans, David J. Rowlands, Vincenzo Crescente, and Claude P. Muller
- Subjects
0301 basic medicine ,Influenza vaccine ,Recombinant Fusion Proteins ,viruses ,lcsh:Biotechnology ,Protein domain ,Hemagglutinins, Viral ,Hemagglutinin (influenza) ,Antibodies, Viral ,complex mixtures ,Pichia ,Virus ,Pichia pastoris ,law.invention ,Long alpha helix ,Mice ,03 medical and health sciences ,Antigen ,law ,lcsh:TP248.13-248.65 ,Animals ,Mice, Inbred BALB C ,biology ,Influenza A Virus, H3N2 Subtype ,Virion ,virus diseases ,Tandem-core ,Virus-like particles ,biology.organism_classification ,Hepatitis B Core Antigens ,Virology ,Yeast ,3. Good health ,030104 developmental biology ,Influenza Vaccines ,Recombinant DNA ,biology.protein ,Female ,Research Article ,Biotechnology - 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. Electronic supplementary material The online version of this article (10.1186/s12896-017-0396-8) contains supplementary material, which is available to authorized users.
- Published
- 2017
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