Deletion of a major neutralizing epitope of human papillomavirus type 16 virus-like particles.
Human papillomavirus type 16 (HPV-16) is a major cause of human cancer. Effective prophylactic vaccines are based on type-specific neutralizing antibodies. A major neutralizing epitope has been defined by the monoclonal antibody H16.V5. To investigate the importance of this epitope for overall immunogenicity of HPV-16, HPV-16 virus-like particles devoid of the H16.V5 epitope were engineered by site-directed mutagenesis of ten non-conserved, surface-exposed residues. Removal of the H16.V5-defined epitope had only a marginal effect on antigenic reactivity with antibodies in sera from infected subjects, but affected immunogenicity in experimental immunization of mice, with reduced induction of both antibody responses and CTL responses.
Ryding
J
J
Department of Medical Microbiology, Malmö University Hospital, Lund University, UMAS, S-205 02 Malmö, Sweden.
Dahlberg
L
L
Active Biotech Research AB, Lund, Sweden.
Wallen-Öhman
M
M
Active Biotech Research AB, Lund, Sweden.
Dillner
J
J
Department of Medical Microbiology, Malmö University Hospital, Lund University, UMAS, S-205 02 Malmö, Sweden.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D000939:Epitopes; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16