title: GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.
abstract: The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.
authors.affiliation: TRIA Bioscience Corp, Seattle, Washington, United States of America.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Clegg
authors.affiliation: TRIA Bioscience Corp, Seattle, Washington, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Roque
authors.affiliation: TRIA Bioscience Corp, Seattle, Washington, United States of America.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Perrone
authors.affiliation: CaroGen Corporation, Hamden, Connecticut, United States of America.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rininger
authors.affiliation: Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Bowen
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004285:Dogs; D004338:Drug Combinations; D004655:Emulsions; D005260:Female; D005289:Ferrets / Q000276:immunology / Q000821:virology; D006801:Humans; D007109:Immunity / Q000187:drug effects; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D058873:Pandemics; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D004655:Emulsions; C000592475:GLA-AF adjuvant; D007252:Influenza Vaccines; D008050:Lipid A; D015060:1,2-Dipalmitoylphosphatidylcholine