Synthetic hepatitis B virus vaccine including both T cell and B cell determinants
AssigneeScripps Clinic and Research Foundation
InventorsDavid R. Milich, Frank V. Chisari
Life of this patent
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Abstract
Chemically synthesized polypeptides include amino acid residue sequences that substantially correspond to the amino acid residue sequences of T cell and B cell determinant portions of a natural, pathogen-related protein, in particular, a hepatitis B virus surface antigen (HBsAg). When administered to a host alone, as polymers or as carrier-bound conjugates, the polypeptides induce the proliferation of thymus-derived cells in hosts primed against hepatitis B virus.
Claims19
A vaccine against infection by hepatitis B virus comprising:
- (a) an effective amount of a synthetic polypeptide having an amino acid residue sequence taken from left to right and in the direction from amino-terminus to carboxy-terminus, and represented by the formula:
- ThrLysProSerAspGlyAsnCysThrCysIleProIleProSer;
- (b) an effective amount of at least one synthetic polypeptide having an amino acid residue sequence taken from left to right and in the direction from amino-terminus to carboxy-terminus selected from the group consisting of:
- PheProGlySerSerThrThrSerThrGlyProCysArgThrCys MetThrThrAlaGlnGlyThrSerMetTyrProSerCys;
- MetThrThrAlaGlnGlyThrSerMetTyrProSerCys;
- IleProGlySerThrThrThrSerThrGlyProCysLysThrCys ThrThrProAlaGlnGlyAsnSerMetPheProSerCys;
- ThrThrProAlaGlnGlyAsnSerMetPheProSerCys;
- and CysProLeuIleProGlySerThrThrThrSerThrGlyPro CysLysThrCysThrThrProAlaGlnGlyAsnSerMet PheProSerCys;
- and
- (c) a physiologically tolerable diluent,
- said vaccine when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus, and said vaccine protecting the host from hepatitis B viral infection.
A vaccine against infection by hepatitis B virus comprising an effective amount of a synthetic polypeptide having an amino acid residue sequence shorter than that of hepatitis B virus surface antigen that immunologically corresponds substantially to limited portions of an amino acid residue sequence of the hepatitis B virus surface antigen, said limited portions being (a) from about positions 140 to 154 and (b) from about positions 110 to 137 from the amino-terminus thereof, and a physiologically tolerable diluent, said vaccine when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus and said vaccine protecting the host from hepatitis B viral infection.
A vaccine against infection by hepatitis B virus comprising an effective amount of a synthetic polypeptide having an amino acid residue sequence shorter than that of hepatitis B virus surface antigen that immunologically corresponds substantially to a limited portion of an amino acid residue sequence of a natural pathogen-related protein encoded by a hepatitis B virus surface antigen, said limited portion being from about positions 110 to 154 from the amino-terminus thereof, and a physiologically tolerable diluent, said vaccine when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus and said vaccine protecting the host from hepatitis B viral infection.
A vaccine against infection by hepatitis B virus comprising an effective amount of a synthetic multimer in a physiologically tolerable diluent, said synthetic multimer comprising a plurality of polypeptide repeating units including
- (a) an amino acid residue sequence taken from left to right and in the direction from amino-terminus to carboxy-terminus, and represented by the formula:
- ThrLysProSerAspGlyAsnCysThrCysIleProIleProSer;
- and
- (b) at least one amino acid residue sequence taken from left to right and in the direction from amino-terminus to carboxy-terminus selected from the group consisting of:
- PheProGlySerSerThrThrSerThrGlyProCysArgThrCys MetThrThrAlaGlnGlyThrSerMetTyrProSerCys;
- MetThrThrAlaGlnGlyThrSerMetTyrProSerCys;
- IleProGlySerThrThrThrSerThrGlyProCysLysThrCys ThrThrProAlaGlnGlyAsnSerMetPheProSerCys;
- ThrThrProAlaGlnGlyAsnSerMetPheProSerCys;
- and CysProLeuIleProGlySerThrThrThrSerThrGlyPro CysLysThrCysThrThrProAlaGlnGlyAsnSerMet PheProSerCys;
- wherein at least two Cys residues are present and said synthetic multimer contains at least one intramolecular cystine disulfide bond formed from at least two of the Cys residues present, said vaccine when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus, and said vaccine protecting the host from hepatitis B viral infection.
A vaccine against infection by hepatitis B virus comprising a physiologically tolerable diluent having dispersed therein (i) an effective amount of a synthetic polypeptide having an amino acid residue sequence that immunologically corresponds substantially to a portion of an amino acid residue sequence of the hepatitis B virus surface antigen from about positions 110 to 137 from the amino-terminus thereof and (ii) an effective amount of a synthetic polypeptide having an amino acid residue sequence taken from left to right and in the direction from amino-teminus to carboxy-teminus, and represented by the formula:
- ThrLysProSerAspGlyAsnCysThr CysIleProIleProSer;
- said vaccine, when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus and said vaccine protecting the host from hepatitis B viral infection.
A vaccine against infection by hepatitis B virus comprising a physiologically tolerable diluent having dispersed therein an effective amount of a synthetic polypeptide having an amino acid residue sequence taken from left to right and in the direction from amino-terminus to carboxy-terminus, and represented by the formula:
- Phe(Ile)ProGlySerSer(Thr)ThrThrSerThr GlyProCysArg(Lys)ThrCysMet(Thr)ThrThr (Pro)AlaGlnGlyThr(Asn)SerMetTyr(Phe) ProSerCysCysCysThrLysProSerAspGlyAsn CysThrCysIleProIleProSer,
- wherein each amino acid residue in parentheses is an alternative to the immediately preceding amino acid residue, said vaccine, when introduced into a host, being capable of inducing the production of antibodies and the proliferation of thymus-derived cells in the host, said antibodies immunoreacting with said hepatitis B virus and said vaccine protecting the host from hepatitis B viral infection.
Dependencies are inferred from the claim text.