One of the open reading frames on hepatitis B virus (HBV)
DNA comprises the coding region (designated the env gene) for the
virus envelope proteins. Studies on
messenger RNA transcription suggest that this gene has the potential to code for three related
proteins: (1) a
protein of 226
amino acids identified as a major
protein constituent of the HBV envelope, termed S-
protein; (2) a
protein with 55 additional
amino acids at the N-terminal coded for by a portion of the env gene upstream of the S-gene (pre-S); (3) a
protein corresponding to the entire env gene (pre-S + S). Synthetic
peptides from the N-terminals of
proteins (2) and (3), and
antisera to them have been used to study the occurrence and properties of pre-S sequences. The results presented here provide unambiguous evidence that all three env encoded
proteins are present in HBV particles; synthetic
peptides corresponding to the gene encoding pre-S are highly immunogenic and can be used in diagnostic tests for detection in human sera of
antibodies preferentially recognizing HBV; such
antibodies, specific for pre-S determinants, are elicited during
hepatitis B infection and by immunization with HBV
proteins (2) and (3); the
hepatitis B vaccine licensed in the United States does not contain
pre-S proteins; and the
pre-S proteins of the HBV envelope contain domains specifically recognized by liver cells. These findings suggest that pre-S determinants are important in virus-neutralizing responses and should be present in HBV
vaccines.