Characterization of HPV16 L1 loop domains in the formation of a type-specific, conformational epitope.
BACKGROUND
Virus-like particles (VLPs) formed by the human papillomavirus (HPV) L1 capsid protein are currently being tested in clinical trials as prophylactic vaccines against genital warts and cervical cancer. The efficacy of these vaccines is critically dependent upon L1 type-specific conformational epitopes. To investigate the molecular determinants of the HPV16 L1 conformational epitope recognized by monoclonal antibody 16A, we utilized a domain-swapping approach to generate a series of L1 proteins composed of a canine oral papillomavirus (COPV) L1 backbone containing different regions of HPV16 L1.


RESULTS
Gross domain swaps, which did not alter the ability of L1 to assemble into VLPs, demonstrated that the L1 N-terminus encodes at least a component of the 16A antigenic determinant. Finer epitope mapping, using GST-L1 fusion proteins, mapped the 16A epitope to the L1 variable regions I and possibly II within the N-terminus.


CONCLUSIONS
These results suggest that non-contiguous loop regions of L1 display critical components of a type-specific, conformational epitope.
Olcese
Vanessa A
VA
Department of Pathology, Georgetown University Medical Center, Washington, DC 20057, USA. olcesev@georgetown.edu
Chen
Yan
Y
Schlegel
Richard
R
Yuan
Hang
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry*; D001666:Binding Sites, Antibody; D036022:Capsid Proteins; D022801:Complementarity Determining Regions / Q000276:immunology; D004285:Dogs / Q000821:virology; D000939:Epitopes / Q000737:chemistry; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology*; D027383:Papillomaviridae / Q000737:chemistry / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D013045:Species Specificity; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology; D014771:Virion / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D036022:Capsid Proteins; D022801:Complementarity Determining Regions; D000939:Epitopes; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines