title: Development and preclinical evaluation of an alphavirus replicon vaccine for influenza.
abstract: We used a propagation-defective, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the hemagglutinin (HA) and neuraminidase (NA) proteins from influenza A/Wyoming/03/2003 (H3N2). Efficient production methods were scaled to produce pilot lots of HA VRP and NA VRP and clinical lots of HA VRP. HA VRP-induced high-titered antibody responses in mice, rabbits and rhesus macaques, as measured by ELISA or hemagglutination inhibition (HI) assays, and robust cellular immune responses in mice and rhesus macaques, as measured by IFN-gamma ELISPOT. NA VRP also induced cellular immune responses in mice. A toxicology study with HA VRP and NA VRP in rabbits showed no adverse effects in any parameter. These studies support clinical testing of alphavirus replicon vaccines for influenza.
authors.affiliation: AlphaVax, Inc., 2 Triangle Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Bolyn
authors.initials: B
authors.lastname: Hubby
authors.forename: Todd
authors.initials: T
authors.lastname: Talarico
authors.forename: Maureen
authors.initials: M
authors.lastname: Maughan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Reap
authors.forename: Peter
authors.initials: P
authors.lastname: Berglund
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Kamrud
authors.forename: Laura
authors.initials: L
authors.lastname: Copp
authors.forename: Whitney
authors.initials: W
authors.lastname: Lewis
authors.forename: Chad
authors.initials: C
authors.lastname: Cecil
authors.forename: Pamela
authors.initials: P
authors.lastname: Norberg
authors.forename: Jordan
authors.initials: J
authors.lastname: Wagner
authors.forename: Aubrey
authors.initials: A
authors.lastname: Watson
authors.forename: Sarah
authors.initials: S
authors.lastname: Negri
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Burnett
authors.forename: Andrew
authors.initials: A
authors.lastname: Graham
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Smith
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Chulay
mesh_terms: D000524:Alphavirus / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007111:Immunity, Cellular; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D009439:Neuraminidase / Q000276:immunology*; D011817:Rabbits; D012093:Replicon
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase