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.
Bibliographical noteFunding Information:
The sera from young girls who received Gardasil or Cervarix came from a study funded by the Department of Health Policy Research Programme (National Vaccine Evaluation Consortium, 039/0031; Prof. Elizabeth Miller). The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health. We are indebted to Prof. John T. Schiller and Dr. Chris Buck (National Cancer Institute, Bethesda, U.S.A.) for access to the 31pSheLL clone.
© The Author(s) 2016.