Development of neutralizing monoclonal antibodies for oncogenic humanpapillomavirus types 31, 33, 45, 52, and 58.

摘要

Human papillomavirus (HPV) is the etiological agent for all cervical cancers, asignificant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalentoncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11,responsible for 90% of genital warts. The vaccines are comprised of recombinantlyexpressed major capsid proteins that self-assemble into virus-like particles(VLPs) and prevent infection by eliciting neutralizing antibodies. Adding theother frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccinewould increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodiesto these five additional oncogenic HPV types, and the selection of antibody pairsthat were high affinity and type specific and recognized conformation-dependentneutralizing epitopes. Such characteristics make these antibodies useful toolsfor monitoring the production and potency of a prototype vaccine as well asmonitoring vaccine-induced immune responses in the clinic.