title: The DE and FG loops of the HPV major capsid protein contribute to the epitopes of vaccine-induced cross-neutralising antibodies.
abstract: The human papillomavirus (HPV) vaccines consist of major capsid protein (L1) virus-like particles (VLP) and are highly efficacious against the development of cervical cancer precursors attributable to oncogenic genotypes, HPV16 and HPV18. A degree of vaccine-induced cross-protection has also been demonstrated against genetically-related genotypes in the Alpha-7 (HPV18-like) and Alpha-9 (HPV16-like) species groups which is coincident with the detection of L1 cross-neutralising antibodies. In this study the L1 domains recognised by inter-genotype cross-neutralising antibodies were delineated. L1 crystallographic homology models predicted a degree of structural diversity between the L1 loops of HPV16 and the non-vaccine Alpha-9 genotypes. These structural predictions informed the design of chimeric pseudovirions with inter-genotype loop swaps which demonstrated that the L1 domains recognised by inter-genotype cross-neutralising antibodies comprise residues within the DE loop and the late region of the FG loop. These data contribute to our understanding of the L1 domains recognised by vaccine-induced cross-neutralising antibodies. Such specificities may play a critical role in vaccine-induced cross-protection.
authors.affiliation: Virus Reference Department, Public Health England, London, UK.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Bissett
authors.affiliation: Virus Reference Department, Public Health England, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Godi
authors.affiliation: Virus Reference Department, Public Health England, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Beddows
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000737:chemistry / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000276:immunology; D006801:Humans; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D017433:Protein Structure, Secondary
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D053918:Papillomavirus Vaccines