Synthetic hepatitis B virus vaccine including both T cell and B cell determinants

Claim 2

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.

Claim 3

The vaccine according to claim 1 wherein said physiologically tolerable diluent is a member of the group consisting of water, saline and an adjuvant.

Claim 4

The vaccine according to claim 1 wherein said synthetic polypeptides are bound to a carrier.

Claim 5

The vaccine according to claim 1 wherein said carrier is selected from the group consisting of keyhole limpet hemocyanin, keyhole limpet hemocyanin in incomplete Freund's adjuvant, alum, keyhole limpet hemocyanin-alum absorbed, keyhole limpet hemocyanin-alum absorbed-pertussis, edestin, thyroglobulin, tetanus toxoid, tetanus toxoid in incomplete Freund's adjuvant, cholera toxoid and cholera toxoid in incomplete Freund's adjuvant.

Claim 6

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.

Claim 7

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.

Claim 8

The vaccine according to claim 5 wherein the synthetic polypeptide includes the sequences of amino acid residues taken from left to right and in the direction from amino-terminus to carboxy-terminus, and represented by the formulae: ThrLysProSerAspGlyAsnCysThrCysIleProIleProSer; and Phe(Ile)ProGlySerSer(Thr)ThrThrSerThrGly ProCysArg(Lys)ThrCysMet(Thr)ThrThr(Pro)Ala GlnGlyThr(Asn)SerMetTyr(Phe)ProSerCys wherein each amino acid residue in parentheses is an alternative to the immediately preceding amino acid residue.

Claim 9

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.

Claim 10

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.

Claim 11

The vaccine according to claim 7 wherein the synthetic polypeptide includes the sequence of amino acid residues taken from left to right and in the direction from amino-terminus to carboxy-terminus, and represented by the formula: Phe(Ile)ProGlySerSer(Thr)ThrThrSerThrGly ProCysArg(Lys)ThrCysMet(Thr)ThrThr(Pro)Ala GlnGlyThr(Asn)SerMetTyr(Phe)ProSerCysCysCys ThrLysProSerAspGlyAsnCysThrCysIleProIleProSer wherein each amino acid residue in parentheses is an alternative to the immediately preceding amino acid residue.

Claim 12

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.

Claim 13

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.

Claim 14

The vaccine according to claim 9 wherein said physiologically tolerable diluent is a member of the group consisting of water, saline and an adjuvant.

Claim 15

The vaccine according to claim 9 wherein said synthetic multimer is bound to a carrier.

Claim 16

The vaccine according to claim 9 wherein said carrier is selected from the group consisting of keyhole limpet hemocyanin, keyhole limpet hemocyanin in incomplete Freund's adjuvant, alum, keyhole limpet hemocyanin-alum absorbed, keyhole limpet hemocyanin-alum absorbed-pertussis, edestin, thyroglobulin, tetanus toxoid, tetanus toxoid in incomplete Freund's adjuvant, cholera toxoid and cholera toxoid in incomplete Freund's adjuvant.

Claim 17

The vaccine according to claim 9 wherein the intramolecular cystine disulfide bond of said synthetic multimer is an intrapolypeptide disulfide bond.

Claim 18

The vaccine according to claim 9 wherein the polypeptide repeating units of said synthetic multimer are bonded together head-to-tail through an amide bond formed between the amine group of the amino-terminal residue of a first polypeptide repeating unit and the carboxyl group of the carboxy-terminal residue of a second polypeptide repeating unit.

Claim 19

The vaccine according to claim 14 wherein said synthetic multimer contains about two to about three of said polypeptide repeating units.

Claim 20

The vaccine according to claim 9 wherein the intramolecular cystine disulfide bond of said synthetic multimer is an interpolypeptide disulfide bond.

Claim 21

The vaccine according to claim 16 wherein the polypeptide repeating units of said synthetic multimer are bonded together by said interpolypeptide cystine disulfide bond formed between the Cys residues of said polypeptide.

Claim 22

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.

Claim 23

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.

Claim 24

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.

Claim 25

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.