Epitopes described in "Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees."

Article Authors:Pei Zhang; Mei-Ying W Yu; Richard Venable; Harvey J Alter; J Wai-Kou Shih
Article Title:Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees.
Reference Detail
Reference ID:1003519
Abstract:Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present in ad subtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority of ay subtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype "d" epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants.
Affiliations:Division of Hematology and Laboratory of Biophysics, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. pei.zhang@fda.hhs.gov.
Reference Type:Literature
PubMed ID:16757558
Journal:Proc Natl Acad Sci U S A
Journal Volume:103
Article Pages:9214-9
Journal ISSN:0027-8424
Article Chemical List:Antibodies, Monoclonal;Epitopes;Peptides
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Monoclonal(immunology); Antibody Specificity; Crystallography, X-Ray; Epitopes; Hepatitis B(immunology); Hepatitis B virus(genetics; immunology); Models, Molecular; Molecular Sequence Data; Pan troglodytes; Peptides(chemistry; genetics; metabolism); Protein Conformation; Sequence Alignment
Curation Last Updated:2015-06-05 00:46:21