IN-VITRO INFECTION AND TYPE-RESTRICTED ANTIBODY-MEDIATED NEUTRALIZATION OF AUTHENTIC HUMAN-PAPILLOMAVIRUS TYPE-16

Human papillomavirus type 16 (HPV-16) is strongly associated with the development of cervical cancer. Studies of model systems with animal p apillomaviruses have demonstrated the importance of neutralizing antib odies in preventing papillomavirus-associated disease. The assessment of neutralizing antibody responses against HPV-16, previously hampered by the lack of a viral source, was enabled by the recent propagation of an HPV-16 stock in xenografted severe combined immunodeficiency (SC ID) mice. HPV-16 infection of an immortalized human keratinocyte cell line was demonstrated by detection of an HPV-16-specific spliced mRNA amplified by reverse transcriptase PCR. Infection was blocked by prein cubation of the virus with antiserum generated against HPV-16 virus-li ke particles (VLPs) composed of the major capsid protein, L1. To exami ne potential cross-neutralizing activity among the different genital H PV types, rabbit antisera to L1 VLPs corresponding to HPV-6, -11, -18, -31, -33, -35, -39, and -45 were assayed for the ability to block the HPV-16 infection of cultured cells. Antiserum raised against HPV-33 b l VLPs was the only heterologous antiserum which inhibited HPV-16 infe ction. Thus, a neutralization assay for HPV-16 may help to characteriz e the components required to compose a broadly efficacious genital HPV vaccine.