title: Cross-neutralization potential of native human papillomavirus N-terminal L2 epitopes.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Conway
authors.forename: Linda
authors.initials: L
authors.lastname: Cruz
authors.forename: Samina
authors.initials: S
authors.lastname: Alam
authors.forename: Neil David
authors.initials: ND
authors.lastname: Christensen
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology; D014771:Virion / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D014765:Viral Vaccines