Neutralization of human papillomavirus (HPV) pseudovirions: A novel and efficient approach to detect and characterize HPV neutralizing antibodies

Mark D. Yeager, Miguel Aste-Amezaga, Darron R. Brown, Melissa M. Martin, Mayur J. Shah, James C. Cook, Neil D. Christensen, Chris Ackerson, Robert S. Lowe, Judy F. Smith, Paul Keller, Kathrin U. Jansen

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

The development of vaccines against human papillomaviruses (HPVs) has long been hampered by the inability to grow HPVs in tissue culture and the lack of an efficient neutralization assay. To date, less than 10% of more than 100 different HPV types can be grown in athymic and "SCID" mouse xenograft systems or raft culture systems. Recently, the in vitro generation of HPV pseudovidons and their use in neutralization assays were demonstrated. The major shortcomings of the current approaches to HPV neutralization are the lack of HPV virions for most types for the xenograft methods and the timeconsuming and inefficient generation of infective pseudovirions for the latter methods, which precludes their use in large-scale HPV clinical trials or epidemiological studies. We describe here a novel and efficient approach to generating pseudovirions in which HPV virus-like particles (VLPs) are coupled to the β-lactamase gene as a reporter. We show that it is not necessary to encapsidate the reporter gene constructs into the pseudovirions. Using sera from human volunteers immunized with HPV-11 VLPs expressed in yeast, we demonstrate that our novel neutralization assay compares favorably with the athymic mouse neutralization assay. Furthermore, our assay was used to define neutralizing monoclonal antibodies to HPV-6, which were previously unknown.

Original languageEnglish (US)
Pages (from-to)570-577
Number of pages8
JournalVirology
Volume278
Issue number2
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Virology

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    Yeager, M. D., Aste-Amezaga, M., Brown, D. R., Martin, M. M., Shah, M. J., Cook, J. C., Christensen, N. D., Ackerson, C., Lowe, R. S., Smith, J. F., Keller, P., & Jansen, K. U. (2000). Neutralization of human papillomavirus (HPV) pseudovirions: A novel and efficient approach to detect and characterize HPV neutralizing antibodies. Virology, 278(2), 570-577. https://doi.org/10.1006/viro.2000.0674