title: Systematic development of a block copolymer adjuvant for trivalent influenza virus vaccine.
abstract: The current influenza virus vaccines induce systemic humoral immunity and short lived cellular immunity in young adults. Unfortunately these vaccines are only 50% efficacious in the elderly (> 65 years) and high risk groups of the very young. The use of a vaccine adjuvant to correct this deficit would therefore be very beneficial to these population groups. We have developed high molecular weight synthetic non-ionic block copolymers with adjuvant activity. These copolymers are compatible with, and active in, aqueous, physiological formulations in which they spontaneously assemble into 500-3000 nm particles. By varying both the molecular weight and the proportions of hydrophilic and hydrophobic components of the molecule, we have designed the optimal copolymer adjuvant for use with influenza hemagglutinin. This copolymer, termed CRL-1005, was investigated for its ability to augment the immune response of mice to the commercially-available human influenza vaccine, Fluogen. Co-formulation of CRL-1005 with the vaccine resulted in markedly increased antibody titres measured by both ELISA and the functional haemagglutination inhibition assay, indicating that critical immunogen epitopes were not destroyed. A single dose of copolymer and vaccine produced both long term rising antibody titres (six months) and primed for a potent secondary response. This high molecular weight copolymer is non-toxic and should therefore be well suited for widespread use.
authors.affiliation: Vaxcel, Inc., Norcross, GA, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Todd
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Balusubramanian
authors.forename: H
authors.initials: H
authors.lastname: Shah
authors.forename: W G
authors.initials: WG
authors.lastname: Henk
authors.forename: L E
authors.initials: LE
authors.lastname: Younger
authors.forename: M J
authors.initials: MJ
authors.lastname: Newman
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000818:Animals; D001672:Biocompatible Materials; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010316:Particle Size; D011092:Polyethylene Glycols; D011108:Polymers
chemical_list: D000276:Adjuvants, Immunologic; D001672:Biocompatible Materials; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011108:Polymers; D011092:Polyethylene Glycols