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Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2.
MedLine Citation:
PMID:  22961598     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The amino terminus of the human papillomavirus minor capsid protein L2 contains a major cross-neutralizing epitope which provides the basis for the development of a broadly protective HPV vaccine. This attainable broad protection would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. In this study we asked whether there are natural variants of the L2 cross-neutralizing epitope and if these variants provide means for immune escape from vaccine induced anti-L2 antibodies. For this we isolatedin silico and in vitro a total of 477 L2 sequences of HPV types 16, 18, 31, 45, 51, 52, and 58. We identified natural L2 epitope variants for HPV 18, 31, 45 and 51. In order to determine whether these variants escape L2-directed neutralization, we generated pseudovirions encompassing the natural variants and tested these in an in vitro neutralization assay using monoclonal and polyclonal antibodies. Our results indicate that natural variants of the L2 major neutralizing epitope are frequent among two different study populations from Germany and Mongolia and in the GenBank database. Of two identified HPV31 L2 single amino acid variants one could be neutralized well while the other variant was neutralized very poorly.We also observed that single amino acid variants of HPV18 and 45 all are neutralized well while a HPV 18 double variant was neutralized at significantly lower rates, indicating that L2 variants have to be accounted for when developing HPV L2-based prophylactic vaccines.
Authors:
Hanna Seitz; Markus Schmitt; Gerd Böhmer; Annette Kopp-Schneider; Martin Müller
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-10
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 UICC.
Affiliation:
Deutsches Krebsforschungszentrum Heidelberg, Germany.
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