Pharmaceutical and immunological evaluation of human papillomavirus viruslike particle as an antigen carrier.
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.
Ionescu
Roxana M
RM
Biologics and Vaccines PR&D, Merck Research Laboratories, Merck & Co., Inc., P.O Box 4, West Point, Pennsylvania 19486-0004, USA.
Przysiecki
Craig T
CT
Liang
Xiaoping
X
Garsky
Victor M
VM
Fan
Jiang
J
Wang
Bei
B
Troutman
Robert
R
Rippeon
Yvette
Y
Flanagan
Elizabeth
E
Shiver
John
J
Shi
Li
L
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
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