title: Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: a phase 1 randomized, double-blind, placebo-controlled, dose-escalation study in healthy adults.
abstract: Recently, we have reported [1,2] on a subunit influenza vaccine candidate based on the recombinant hemagglutinin protein from the A/Indonesia/05/2005 (H5N1) strain of influenza virus, produced it using 'launch vector'-based transient expression technology in Nicotiana benthamiana, and demonstrated its immunogenicity in pre-clinical studies.  Here, we present the results of a first-in-human, Phase 1 randomized, double-blind, placebo-controlled study designed to investigate safety, reactogenicity and immunogenicity of three escalating dose levels of this vaccine, HAI-05, (15, 45 and 90 µg) adjuvanted with Alhydrogel® (0.75 mg aluminum per dose) and the 90 µg dose level without Alhydrogel®. Vaccine was administered intramuscularly in two injections three weeks apart to healthy adults of 18-49 years of age. At all dose levels the vaccine was generally safe and well tolerated, with no reported serious adverse events or  dose-limiting toxicities. Mild local and systemic reactions were observed in all vaccine dose groups and the placebo group and their occurrence was not dose related.  The incidence rates were higher in the groups receiving vaccine with Alhydrogel®.  The immune response elicited by the HAI-05 vaccine was variable with respect to both hemagglutination-inhibition and virus microneutralization antibody titers, with the highest responses observed in the 90 µg unadjuvanted group.
authors.affiliation: Fraunhofer USA, Center for Molecular Biotechnology, Newark, DE 19711, USA. jchichester@fraunhofer-cmb.org
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Green
authors.forename: Mark
authors.initials: M
authors.lastname: Stow
authors.forename: Fudu
authors.initials: F
authors.lastname: Miao
authors.forename: George
authors.initials: G
authors.lastname: Moonsammy
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Streatfield
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins