Binding and neutralization efficiencies of monoclonal antibodies, Fab fragments, and scFv specific for L1 epitopes on the capsid of infectious HPV particles.
We compared the neutralization abilities of individual monoclonal antibodies (MAb) of two large panels reactive with L1 epitopes of HPV-11 or HPV-16. Binding titers were compared using both L1-only VLPs and L1/L2 pseudovirions. While the VLPs were antigenically similar to the pseudovirions, clear differences in the surface exposure of some epitopes were evident with the HPV-16 particles. To determine whether all antibody binding events are equivalent in their neutralizing effect on infectious HPV virions or pseudovirions, the binding and neutralization titers for individual MAbs were used to calculate the relative neutralization efficiency for each antibody. HPV neutralization was achieved by all MAbs capable of strong binding to either linear or conformation-sensitive epitopes on pseudovirus particles. Our data suggest, however, that some L1 epitopes may be more neutralization-sensitive than other surface epitopes, in that successful infection can be blocked by varying degrees of epitope saturation. Additionally, the effective neutralization of virions by several monovalent Fab fragments and single-chain variable fragments (scFv) demonstrates that viral neutralization does not require HPV particle aggregation or L1 crosslinking. Identification of capsid protein structures rich in neutralization-sensitive epitopes may aid in the development of improved recombinant vaccines capable of eliciting effective and long-term antibody-mediated protection against multiple HPV types.
Culp
Timothy D
TD
Gittlen Cancer Research Foundation, Pennsylvania State University, Hershey, PA 17033, USA.
Spatz
Christin M
CM
Reed
Cynthia A
CA
Christensen
Neil D
ND
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology*; D052140:Human papillomavirus 11 / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D007135:Immunoglobulin Variable Region; C094776:L1 protein, Human papillomavirus type 11; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16