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J Virol, February 1998, p. 959-964, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

In Vitro Infection and Type-Restricted Antibody-Mediated Neutralization of Authentic Human Papillomavirus Type 16

Wendy I. White,1,* Susan D. Wilson,1 William Bonnez,2 Robert C. Rose,2 Scott Koenig,1 and Joann A. Suzich1

MedImmune, Inc., Gaithersburg, Maryland 20878,1 and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 146422

Received 24 July 1997/Accepted 3 November 1997

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.

* Corresponding author. Mailing address: 35 W. Watkins Mill Rd., Gaithersburg, MD 20878. Phone: (301) 417-0770. Fax: (301) 527-4200. E-mail: whitew{at}medimmune.com.




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