title: Pharmaceutical and immunological evaluation of human papillomavirus viruslike particle as an antigen carrier.
abstract: We report the preparation and the immunogenicity of a conjugate vaccine obtained by chemically conjugating a variant of the extracellular peptide fragment of influenza type A M2 protein to the human papillomavirus (HPV) viruslike particle (VLP). Conjugates comprised of approximately 4,000 copies of the antigenic peptide per VLP are obtained as the result of the reaction between a C-terminal cysteine residue on the peptide and the maleimide-activated HPV VLP. The resulting conjugates have an average particle size slightly larger than the carrier and present enhanced overall stability against chemical and thermal-induced denaturation. The M2-HPV VLP conjugates lost the binding affinity for anti-HPV conformational antibodies but retained reactivity to a M2-specific monoclonal antibody. The conjugate vaccine formulated with aluminum adjuvant and delivered in two doses of 30-ng peptide was found to be highly immunogenic and conferred good protection against lethal challenge of influenza virus in mice. These results suggest that HPV VLP can be used as a carrier for synthetic or small antigens for the development of subunit vaccines.
authors.affiliation: Biologics and Vaccines PR&D, Merck Research Laboratories, Merck & Co., Inc., P.O Box 4, West Point, Pennsylvania 19486-0004, USA.
authors.forename: Roxana M
authors.initials: RM
authors.lastname: Ionescu
authors.forename: Craig T
authors.initials: CT
authors.lastname: Przysiecki
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liang
authors.forename: Victor M
authors.initials: VM
authors.lastname: Garsky
authors.forename: Jiang
authors.initials: J
authors.lastname: Fan
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Troutman
authors.forename: Yvette
authors.initials: Y
authors.lastname: Rippeon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Flanagan
authors.forename: John
authors.initials: J
authors.lastname: Shiver
authors.forename: Li
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines; D051379:Mice; D008807:Mice, Inbred BALB C; D027383:Papillomaviridae; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016019:Survival Analysis; D014611:Vaccination; D018074:Vaccines, Conjugate; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D007252:Influenza Vaccines; D010446:Peptide Fragments; D018074:Vaccines, Conjugate; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins