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Cross-Neutralization Potential of Native Human Papillomavirus N-Terminal L2 Epitopes

Public Library of Science
Publication Date
DOI: 10.1371/journal.pone.0016405
  • Research Article
  • Biology
  • Microbiology
  • Virology
  • Viral Transmission And Infection
  • Host Cells
  • Viral Entry
  • Viral Immune Evasion
  • Viral Vaccines
  • Viruslike Particles
  • Immunity
  • Medicine
  • Anatomy And Physiology
  • Immune Physiology
  • Antibodies
  • Antigens
  • Clinical Immunology
  • Vaccination
  • Vaccine Development
  • Infectious Diseases
  • Viral Diseases
  • Human Papillomavirus Infection
  • Biology


Background Human papillomavirus (HPV) capsids are composed of 72 pentamers of the major capsid protein L1, and an unknown number of L2 minor capsid proteins. An N-terminal “external loop” of L2 contains cross-neutralizing epitopes, and native HPV16 virions extracted from 20-day-old organotypic tissues are neutralized by anti-HPV16 L2 antibodies but virus from 10-day-old cultures are not, suggesting that L2 epitopes are more exposed in mature, 20-day virions. This current study was undertaken to determine whether cross-neutralization of other HPV types is similarly dependent on time of harvest and to screen for the most effective cross-neutralizing epitope in native virions. Methodology and Principal Findings Neutralization assays support that although HPV16 L2 epitopes were only exposed in 20-day virions, HPV31 or HPV18 epitopes behaved differently. Instead, HPV31 and HPV18 L2 epitopes were exposed in 10-day virions and remained so in 20-day virions. In contrast, presumably due to sequence divergence, HPV45 was not cross-neutralized by any of the anti-HPV16 L2 antibodies. We found that the most effective cross-neutralizing antibody was a polyclonal antibody named anti-P56/75 #1, which was raised against a peptide consisting of highly conserved HPV16 L2 amino acids 56 to 75. Conclusions and Significance This is the first study to determine the susceptibility of multiple, native high-risk HPV types to neutralization by L2 antibodies. Multiple anti-L2 antibodies were able to cross-neutralize HPV16, HPV31, and HPV18. Only neutralization of HPV16 depended on the time of tissue harvest. These data should inform attempts to produce a second-generation, L2-based vaccine.

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