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A hepatitis B virus variant found in the sera of immunised children induces a conformational change in the HBsAg "a" determinant.

Abstract：

:The emergence of variants in the outer envelope proteins of hepatitis B virus (HBV) are found among individuals vaccinated against HBV and asymptomatic carriers of the infection. For example, children in The Gambia vaccinated against hepatitis B may show serological evidence of breakthrough infections, particularly if anti-HBs antibodies induced by the vaccine are low in titre. A single-point mutation at nucleotide 421 of the S gene is associated with such breakthrough infections. In the present study, the antigenicity of variant HBV S protein expressed as HBsAg particles in a vaccinia virus expression system has been characterised using a panel of monoclonal antibodies directed against linear and conformational determinations of the S protein. A cellular ELISA procedure using expressed antigen in Vero cells revealed differences in reactivity using four of the six antibodies that had been raised against the adw subtype of HBV and recognise conformational epitopes in the a determinant. In two instances, an enhanced reactivity for the variant antigen was found, confirming that point mutations in the a determinant of the S protein between residues 139 and 147 may result in significant changes in conformation. These findings also demonstrate that there are distinct antigenic differences between the vaccine strains of HBsAg/ adw subtype and the predominant HBsAg subtype circulating in West Africa. The implications of this work are that serodiagnosis of HBV infections may be unreliable in populations where there is a possibility of variant HBV infections emerging in the face of increasing herd immunity to HBV as a result of vaccination, particularly using monoclonal antibody-based diagnostic tests. Such variants may play a role in the maintenance of HBV infections in endemic regions.

journal_name

J Med Virol

journal_title

Journal of medical virology

authors

Karthigesu VD,Allison LM,Ferguson M,Howard CR

doi

10.1002/(sici)1096-9071(199908)58:4<346::aid-jmv5>

keywords:

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

346-52

issue

eissn

0146-6615

issn

1096-9071

pii

10.1002/(SICI)1096-9071(199908)58:4<346::AID-JMV5>

journal_volume

pub_type

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A hepatitis B virus variant found in the sera of immunised children induces a conformational change in the HBsAg "a" determinant.