Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine

Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Her...

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Published in:	PloS one Vol. 8; no. 10; p. e76571
Main Authors:	Skibinski, David A G, Hanson, Brendon J, Lin, Yufang, von Messling, Veronika, Jegerlehner, Andrea, Tee, Jason Boon Sern, Chye, De Hoe, Wong, Steven K K, Ng, Amanda A P, Lee, Hui Yin, Au, Bijin, Lee, Bernett T K, Santoso, Lucia, Poidinger, Michael, Fairhurst, Anna-Marie, Matter, Alex, Bachmann, Martin F, Saudan, Philippe, Connolly, John E
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 18-10-2013 Public Library of Science (PLoS)
Subjects:	Adjuvants, Immunologic Alum Alum Compounds Aluminum sulfate Animals Antibodies Antibodies, Neutralizing Antibodies, Neutralizing - immunology Antibodies, Viral Antibodies, Viral - immunology Antibody Specificity Antigens Avian flu Bacteriophages Bacteriophages - immunology Biological response modifiers Biotechnology Cell culture Cytokines E coli Epidemics Escherichia coli Escherichia coli - genetics Escherichia coli - immunology Female Ferrets Ferrets - immunology Glycoproteins Hemagglutinin Glycoproteins, Influenza Virus Hemagglutinin Glycoproteins, Influenza Virus - immunology Humans Immunization Immunoglobulin G Immunoglobulin G - immunology Immunoglobulins Immunology Infections Infectious diseases Influenza Influenza A Influenza A Virus, H1N1 Subtype Influenza A Virus, H1N1 Subtype - immunology Influenza Vaccines Influenza Vaccines - immunology Interferon Interferon-gamma Interferon-gamma - biosynthesis Laboratories Life Sciences Lungs Lymphocytes Lymphocytes T Medical research Mice Microbiology and Parasitology Morbidity Neutralizing Orthomyxoviridae Infections Orthomyxoviridae Infections - prevention & control Pandemics RNA, Bacterial RNA, Bacterial - immunology Science Splenocytes T cells T-Cell Antigen Receptor Specificity T-Cell Antigen Receptor Specificity - immunology T-Lymphocyte Subsets T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Th1 Cells Th1 Cells - immunology Th1 Cells - metabolism Vaccines Vaccines, Virus-Like Particle Vaccines, Virus-Like Particle - immunology Virology Virus-like particles Viruses Singapore
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Summary:	Influenza pandemics can spread quickly and cost millions of lives; the 2009 H1N1 pandemic highlighted the shortfall in the current vaccine strategy and the need for an improved global response in terms of shortening the time required to manufacture the vaccine and increasing production capacity. Here we describe the pre-clinical assessment of a novel 2009 H1N1 pandemic influenza vaccine based on the E. coli-produced HA globular head domain covalently linked to virus-like particles derived from the bacteriophage Qβ. When formulated with alum adjuvant and used to immunize mice, dose finding studies found that a 10 µg dose of this vaccine (3.7 µg globular HA content) induced antibody titers comparable to a 1.5 µg dose (0.7 µg globular HA content) of the licensed 2009 H1N1 pandemic vaccine Panvax, and significantly reduced viral titers in the lung following challenge with 2009 H1N1 pandemic influenza A/California/07/2009 virus. While Panvax failed to induce marked T cell responses, the novel vaccine stimulated substantial antigen-specific interferon-γ production in splenocytes from immunized mice, alongside enhanced IgG2a antibody production. In ferrets the vaccine elicited neutralizing antibodies, and following challenge with influenza A/California/07/2009 virus reduced morbidity and lowered viral titers in nasal lavages.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC3799843 Conceived and designed the experiments: DAGS BJH YL VvM AJ AM MFB PS JEC. Performed the experiments: DAGS BJH YL VvM AJ JBST DHC SKKW AAPN HYL BA A-MF. Analyzed the data: DAGS BJH VvM BA BTKL LS MP. Contributed reagents/materials/analysis tools: AJ MFB PS. Wrote the paper: DAGS JEC. Current address: University Hospital ZŸrich, ZŸrich, Switzerland Competing Interests: The authors declare that Philippe Saudan is currently employed by Cytos Biotechnology AG and holds stocks or stock options in Cytos Biotechnology AG. Andrea Jegerlehner and Martin Bachmann are former employees of Cytos Biotechnology AG but are no longer affiliated with this company. Andrea Jegerlehner holds stocks or stock options in Cytos Biotechnology AG. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. Current address: Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0076571