Monoclonal antibodies to various epitopes of hepatitis B surface antigen inhibit hepatitis B virus infection
Background and Aim Antibodies against the “a” determinant of hepatitis B surface antigen (HBsAg) are able to neutralize circulating hepatitis B virus (HBV) particles and prevent HBV infection. It has been proposed that a single amino acid exchange may allow the virus to escape the immune response. W...
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Published in | Journal of gastroenterology and hepatology Vol. 29; no. 5; pp. 1083 - 1091 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
Blackwell Publishing Ltd
01.05.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Background and Aim
Antibodies against the “a” determinant of hepatitis B surface antigen (HBsAg) are able to neutralize circulating hepatitis B virus (HBV) particles and prevent HBV infection. It has been proposed that a single amino acid exchange may allow the virus to escape the immune response. We used a set of monoclonal antibodies (MAbs) to investigate whether a single mutation may account for virus escape from humoral immunity.
Methods
Nine murine HBsAg‐specific MAbs were raised. Reactivity of all antibodies with 14 recombinant mutants of HBsAg was assessed by ELISA. HBV infection of HepaRG cells was used to evaluate viral neutralization capacity of MAbs in vitro.
Results
All MAbs were able to inhibit the establishment of HBV infection in a dose‐dependent fashion, but recognition of HBsAg variants varied. The MAbs were classified into three subgroups based on their pattern of reactivity to the HBsAg variants. Accordingly, three MAbs showed weak reactivity (< 40%) to variants with mutations within the first loop of “a” determinant, five MAbs displayed negligible binding to variants with mutations within the second loop, and one MAb lost its binding to variants having mutations in both loops of the “a” determinant.
Conclusions
Our results indicate that antibodies against different epitopes of the “a” determinant of HBsAg are able to neutralize HBV. It seems that mutations within a single or a limited number of amino acids within this determinant can hardly result in viral escape. These results have important implications for the development of antibody‐based therapies against HBV. |
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Bibliography: | ark:/67375/WNG-4L5KGJ55-2 Avicenna Research Institute Iran National Science Foundation istex:D9AC66EA1B538AE020775DB248A2BEB3E0F10345 ArticleID:JGH12483 This study was supported in part by grants from Avicenna Research Institute and Iran National Science Foundation. Competing interests Funding The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0815-9319 1440-1746 |
DOI: | 10.1111/jgh.12483 |