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 language | English |
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Article number | 000829 |
Pages (from-to) | 1755-1761 |
Number of pages | 7 |
Journal | Journal of General Virology |
Volume | 98 |
Issue number | 7 |
DOIs | |
Publication status | Published - 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