title: Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine.
abstract: 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.
authors.affiliation: ASTAR Program in Translational Research on Infectious Disease, Agency for Science, Technology and Research, Singapore ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore.
authors.forename: David A G
authors.initials: DA
authors.lastname: Skibinski
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Hanson
authors.forename: Yufang
authors.initials: Y
authors.lastname: Lin
authors.forename: Veronika
authors.initials: V
authors.lastname: von Messling
authors.forename: Andrea
authors.initials: A
authors.lastname: Jegerlehner
authors.forename: Jason Boon Sern
authors.initials: JB
authors.lastname: Tee
authors.forename: De Hoe
authors.initials: de H
authors.lastname: Chye
authors.forename: Steven K K
authors.initials: SK
authors.lastname: Wong
authors.forename: Amanda A P
authors.initials: AA
authors.lastname: Ng
authors.forename: Hui Yin
authors.initials: HY
authors.lastname: Lee
authors.forename: Bijin
authors.initials: B
authors.lastname: Au
authors.forename: Bernett T K
authors.initials: BT
authors.lastname: Lee
authors.forename: Lucia
authors.initials: L
authors.lastname: Santoso
authors.forename: Michael
authors.initials: M
authors.lastname: Poidinger
authors.forename: Anna-Marie
authors.initials: AM
authors.lastname: Fairhurst
authors.forename: Alex
authors.initials: A
authors.lastname: Matter
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: Philippe
authors.initials: P
authors.lastname: Saudan
authors.forename: John E
authors.initials: JE
authors.lastname: Connolly
mesh_terms: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D001435:Bacteriophages / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D005260:Female; D005289:Ferrets / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012329:RNA, Bacterial / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012329:RNA, Bacterial; D058425:Vaccines, Virus-Like Particle; C041524:aluminum sulfate; D007371:Interferon-gamma