Strategically modified hepatitis B core proteins and their derivatives

DETAILED DESCRIPTION The present invention relates to a strategically modified hepatitis B core (HBc) protein that is linked to a pendent hapten through chemically-reactive amino acid residue inserted into the HBc sequence.
The contemplated strategic modification of HBc is an insert mutation of the HBc protein.
A contemplated insert is 1 to about 40 amino acid residues in length, preferably 1 to 10 amino acid residues in length, and includes a chemically-reactive amino acid residue.
The insert is provided to the region corresponding to amino acid residues about 50 to about 100 of the hepatitis B core protein sequence shown in SEQ ID NO:2.
The preferred region of insertion corresponds to the hepatitis B core protein immunodominant loop region at about amino acid residue 70 to about 90, more preferably the loop tip region at about amino acid 78 to about 82 and most preferably at amino acid 78 to amino acid 80.
Such an introduced chemically-reactive amino acid residue is characterized in that it has a chemically-reactive side chain that provides a chemical group for pendently linking the strategically modified HBc to the hapten.
Typically, the chemically-reactive amino acid residue is a lysine, cysteine, or histidine residue or a carboxyl-containing residue such as aspartic acid or glutamic acid, preferably lysine or a carboxyl-containing residue, and most preferably lysine.
The hapten bonded to the chemically-reactive amino acid residue is any compound of interest for generating an immune response, and is typically a B cell determinant.
Preferably, the hapten is a polypeptide hapten, a carbohydrate hapten, or a non-peptidal/non-saccharidal (chemical) hapten.
In one embodiment of the invention, the hapten is a pathogen-related hapten, such as a B cell determinant of a pathogen.
In another embodiment of a strategically modified hepatitis B core protein conjugate, the strategically modified hepatitis B core protein also has a T cell stimulating amino acid residue sequence operatively linked to the carboxy terminus of the hepatitis B core amino acid sequence