CHARACTERIZATION OF UNUSUAL ESCAPE VARIANTS OF HEPATITIS-B VIRUS ISOLATED FROM A HEPATITIS-B SURFACE ANTIGEN-NEGATIVE SUBJECT

Hepatitis B virus DNA was extracted from serial serum samples of a hep atitis B surface antigen-negative patient with antibodies to the core protein as the only marker of an infection with hepatitis B virus. Thi s patient showed no symptoms of hepatic injury. Sequencing of the ampl ified viral DNA demonstrated multiple amino acid changes clustering in surface-exposed regions of the surface protein. Synthesis and associa tion of the middle (M) and small (S) surface proteins could be shown i n vitro. The variant surface antigens were recognized neither by monoc lonal antibodies to the surface antigen nor by the vaccinee's sera. Co nsequences for hepatitis B surface antigen testing and vaccine develop ment are discussed.