A deletion and point mutation study of the human papillomavirus type 16 major capsid gene

Varsani, A., Williamson, A. L., Jaffer, M. A., & Rybicki, E. P. (2006) A deletion and point mutation study of the human papillomavirus type 16 major capsid gene. Virus Research, 122(1-2), pp. 154-163.

View at publisher

Abstract

Recombinant human papillomavirus (HPV) virus-like particles (VLPs) made from the major capsid protein L1 are promising vaccine candidates for use as vaccines against genital and other HPV infections, and particularly against HPV-16. However, HPV-16 genotype variants have different binding affinities for neutralising mouse Mabs raised against HPV-16 L1 VLPs. This paper analyses, using a panel of well-characterised Mabs, the effects on the antigenicity of various C- and N-terminal deletants of HPV-16 L1 made in insect cells via recombinant baculovirus, of an A → T mutation at residue 266 (A266T), and of a C → G mutation at conserved position 428 (C428G). The effects of these changes on assembly of the variant L1s were studied by electron microscopy. Binding of Mab H16:E70 to A266T was reduced by almost half in comparison to wild type L1. Retention of the C-terminal region 428-483 was critical for the binding of conformation-specific Mabs (H16:V5, H16:E70, H16:U4 and H16:9A) whereas deletion of the nuclear localisation signal (NLS) or the C428G mutation or an N-terminal deletion (residues 2-9) did not affect the antigenicity. The N-terminal deletion resulted in a mixed population of 30 and 55 nm VLPs, which differs from the same construct expressed in Escherichia coli, whereas pentamer aggregates resulted from deletion of the 428-465 region or the C428G mutation. The results have implications both for considering use of single-genotype HPV vaccines, and for design of novel second-generation vaccines. © 2006 Elsevier B.V. All rights reserved.

Impact and interest:

16 citations in Scopus
Search Google Scholar™
16 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 54966
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996): 9
Export Date: 12 November 2012
Source: Scopus
Keywords: Antigenicity, Deletion, HPV-16, L1, Papillomavirus, VLP
DOI: 10.1016/j.virusres.2006.07.012
Deposited On: 20 Nov 2012 02:46
Last Modified: 20 Nov 2012 02:57

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page