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.

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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.

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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

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