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 papillomaviruses have demonstrated the importance of neutralizing antibodies 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 (SCID) 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 preincubation of the virus with antiserum generated against HPV-16 virus-like particles (VLPs) composed of the major capsid protein, L1. To examine potential cross-neutralizing activity among the different genital HPV 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 L1 VLPs was the only heterologous antiserum which inhibited HPV-16 infection. Thus, a neutralization assay for HPV-16 may help to characterize the components required to compose a broadly efficacious genital HPV vaccine.
White
W I
WI
MedImmune, Inc., Gaithersburg, Maryland 20878, USA. whitew@medimmune.com
Wilson
S D
SD
Bonnez
W
W
Rose
R C
RC
Koenig
S
S
Suzich
J A
JA
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000517:prevention & control*; D011817:Rabbits; D002583:Uterine Cervical Neoplasms / Q000821:virology
D000914:Antibodies, Viral