Impact of naturally occurring variation in the human papillomavirus (HPV) 33 capsid proteins on recognition by vaccine-induced cross-neutralizing antibodies

Anna Godi, Sara L. Bissett, Elizabeth Miller, Simon Beddows*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

We investigated naturally occurring variation within the major (L1) and minor (L2) capsid proteins of human papillomavirus (HPV) genotype 33. Pseudoviruses (PsV) representing HPV33 lineages A1, A2, A3, B and C exhibited comparable particle-toinfectivity ratios and morphology but demonstrated a decreased sensitivity (A2, A3, B and C) to cross-neutralization by HPV vaccine antibodies compared to the A1 sublineage. Chimeric PsVs demonstrated that these differences in sensitivity were due to polymorphisms in the L1 protein, with little or no influence from variation within the L2 protein. Site-directed mutagenesis of the L1 gene identified the DE loop residue 133 and the FG residue 266 as being critical for conferring this differential sensitivity. The use of HPV33 homology models based upon the HPV16 crystal structure suggested that they are likely to act independently on more than one antibody epitope. These data improve our understanding of the potential impact of natural capsid variation on recognition by vaccine antibodies.

Original languageEnglish
Article number000829
Pages (from-to)1755-1761
Number of pages7
JournalJournal of General Virology
Volume98
Issue number7
DOIs
Publication statusPublished - Jul 2017

Bibliographical note

Funding Information:
The sera from young girls who received Gardasil or Cervarix came from a study funded in part by the UK Department of Health Policy Research Programme (National Vaccine Evaluation Consortium, 039/0031; EM). We are indebted to John T. Schiller and Chris Buck (National Cancer Institute, Bethesda, MD) for access to the psheLL backbone used for the pseudovirus clones. The views expressed in this publication are those of the author(s) and not necessarily those of the UK Department of Health.

Keywords

  • Antibody
  • Human papillomavirus
  • L1
  • L2
  • Lineage
  • Neutralization
  • Vaccine
  • Variant

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