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Genetic backbone modulates phenotype of Hepatitis B Surface Antigen "mutants"

Centre for Infections, Health Protection Agency

¹ E-mail: richard.tedder{at}hpa.org.uk

Hepatitis B virus vaccine and diagnostic escape mutants are a growing concern. The principle target of detection, HBsAg, encoded by S, is completely overlapped by the reverse transcriptase encoding P. With the increased incidence of nucleos(t)ide analogue resistance altering P, the concurrent impact on S must be assessed. HBV DNA from fifty nine HBsAg-positive plasmas was sequenced across the polymerase/surface region and the amino acid sequence of HBsAg inferred. ELISA's were formatted containing individually bound monoclonal antibodies directed against three discrete epitopes on HBsAg. Similar point mutations occurring in different genotypes were shown to influence epitope conformation differently indicating that genetic backbone is a major factor in predicting phenotype. C-terminal changes associated with antiviral resistance were found to modulate epitope profiles of HBsAg. Treatment options which may promote drug resistance should be avoided both to protect antiviral treatment and also to prevent facilitation of vaccine and diagnostic escape mutants.

Received 28 April 2009; accepted 11 September 2009.