Stress protein-peptide complexes as prophylactic and therapeutic vaccines against intracellular pathogens
AssigneeMount Sinai School of Medicine of the City University of New York
InventorPramod K. Srivastava
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Abstract
Disclosed is a family of vaccines that contain stress protein-peptide complexes which when administered to a mammal are operative at initiating in the mammal cytotoxic T cell responses against preselected intracellular pathogens. Also disclosed are methodologies for preparing and administering vaccines containing stress protein-peptide complexes.
Claims153
A composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in a mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said pathogen but not present in said cell when said cell is not infected with said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- a purified mammalian stress protein-peptide complex, said complex comprising
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, but not present in said cell when said cell is not infected with said pathogen.
A method of eliciting in a mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, that causes disease in said mammal, the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said pathogen, and said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said pathogen but not present in said cell when said cell is not infected with said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, that causes disease in said mammal, the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said pathogen, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell infected with said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in an eukaryotic cell transfected with a gene encoding an antigenic determinant of said pathogen but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, that causes disease in said mammal, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said pathogen , and said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell transfected with a gene encoding an antigenic determinant of said pathogen but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, that causes disease in said mammal, the method comprising:
- administering to said mammal a composition comprising,
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said pathogen, said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell transfected with a gene encoding an antigenic determinant of said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- (a) an amount of a purified population of immunogenic human stress protein-peptide complexes sufficient to elicit in a human an immune response against an intracellular pathogen, said population comprising a complex of a human stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said intracellular pathogen but not present in said cell when said cell is not infected with said intracellular pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- a purified human stress protein-peptide complex, said complex comprising
- a human stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with an intracellular pathogen but not present in said cell when said cell is not infected with said intracellular pathogen.
A composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in a mammal an immune response against a virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said virus but not present in said cell when said cell is not infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- a purified mammalian stress protein-peptide complex, said complex comprising
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with a virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), but not present in said cell when said cell is not infected with said virus.
A method of eliciting in a human an immune response against a virus that causes disease in said human, the method comprising:
- administering to said human a composition comprising:
- (a) an amount of a purified population of immunogenic human stress protein-peptide complexes sufficient to elicit in said human an immune response against said virus, said population comprising a complex of
- a human stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said virus but not present in said cell when said cell is not infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a human an immune response against a virus that causes disease in said human, the method comprising:
- administering to said human a composition comprising:
- (a) an amount of a purified population of immunogenic human stress protein-peptide complexes sufficient to elicit in said human an immune response against said virus, said population comprising a complex of
- a human stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against a virus that causes disease in said mammal, said virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said virus, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said virus but not present in said cell when said cell is not infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against a virus that causes disease in said mammal, said virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said virus, said population comprising a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- (a) an amount of a purified population of immunogenic human stress protein-peptide complexes sufficient to elicit in a human an immune response against a virus, said population comprising a complex of a human stress protein noncovalently associated with a peptide that is present in an eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in a mammal an immune response against a virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide that is present in an eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a human an immune response against a virus that causes disease in said human, the method comprising:
- administering to said human a composition comprising,
- (a) an amount of a purified population of immunogenic human stress protein-peptide complex sufficient to elicit in said mammal an immune response against said virus, said population comprising a complex of a human stress protein noncovalently associated with a peptide that is present in a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a human an immune response against a virus that causes disease in said human, the method comprising:
- administering to said human a composition comprising
- (a) an amount of a purified population of immunogenic human stress protein-peptide complex sufficient to elicit in said human an immune response against said virus, said population comprising a complex of
- a human stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against a virus that causes disease in said mammal, said virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said virus, said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against a virus that causes disease in said mammal, said virus selected from the group consisting of hepatitis type A, hepatitis type B, hepatitis type C, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, huntavirus, coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II), the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complex sufficient to elicit in said mammal an immune response against said virus, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A composition comprising:
- a complex of a mammalian stress protein noncovalently bound to an immunogenic peptide, wherein the complex is the product of a process comprising noncovalently complexing in vitro said immunogenic peptide to said stress protein, wherein said immunogenic peptide was obtained by eluting the peptide from a MHC-peptide complex isolated from an infected or transfected cell, in which the peptide is present in said cell infected with a pathogen or transfected with a gene encoding an antigenic determinant of said pathogen, but not present in said cell when said cell is not infected with said pathogen or not transfected with said gene, respectively.
A method of treating an infectious disease in a mammal caused by an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said pathogen, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said pathogen but not present in said cell when said cell is not infected with said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said pathogen and comprising
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell infected with said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said pathogen, and said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell transfected with a gene encoding an antigenic determinant of said pathogen but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by an intracellular pathogen selected from the group consisting of a bacterium, protozoan, fungus and parasite, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said pathogen, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell transfected with a gene encoding an antigenic determinant of said pathogen;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by a virus, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said virus, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell infected with said virus but not present in said cell when said cell is not infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by a virus, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said virus, said population comprising a complex of
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell infected with said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by a virus, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said virus, said population comprising a complex of a mammalian stress protein noncovalently associated with a peptide that is present in a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus but not present in said cell when said cell is not transfected with said gene;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by a virus, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said virus, and comprising
- a mammalian stress protein noncovalently associated with a peptide, said population of complexes having been isolated from a eukaryotic cell transfected with a gene encoding an antigenic determinant of said virus;
- and
- (b) a pharmaceutically acceptable carrier.
A method of eliciting in a mammal an immune response against an intracellular pathogen that causes disease in said mammal, the method comprising:
- administering to said mammal a composition comprising
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes sufficient to elicit in said mammal an immune response against said pathogen, wherein the population of complexes is the product of a process comprising noncovalently complexing in vitro a population of immunogenic peptides to a stress protein, wherein said population of immunogenic peptides comprises immunogenic peptides which were obtained by eluting the peptides from MHC-peptide complexes isolated from a cell infected by said pathogen or transfected with a gene encoding an antigenic determinant of said pathogen, in which the population of immunogenic peptides comprises a peptide that is present in said cell infected with said pathogen or transfected with a gene encoding an antigenic determinant of said pathogen, but not present in said cell when said cell is not infected with said pathogen or not transfected with said gene, respectively;
- and
- (b) a pharmaceutically acceptable carrier.
A method of treating an infectious disease in a mammal caused by an intracellular pathogen, the method comprising:
- administering to said mammal a composition comprising:
- (a) an amount of a purified population of immunogenic mammalian stress protein-peptide complexes therapeutically effective to treat an infectious disease caused by said pathogen, wherein the population of complexes is the product of a process comprising noncovalently complexing in vitro a population of immunogenic peptides to a stress protein, wherein said population of immunogenic peptide comprises immunogenic peptides which were obtained by eluting the peptides from MHC-peptide complexes isolated from a cell infected by said pathogen or transfected with a gene encoding an antigenic determinant of said pathogen, in which the population of immunogenic peptides comprises a peptide that is present in said cell infected with said pathogen or transfected with a gene encoding an antigenic determinant of said pathogen, but not present in said cell when said cell is not infected with said pathogen or not transfected with said gene, respectively;
- and
- (b) a pharmaceutically acceptable carrier.
A purified, immunogenic, noncovalent complex of a mammalian stress protein and an antigenic peptide, which complex is the product of complexing said mammalian stress protein and said antigenic peptide in vitro.
A method for eliciting in a mammal an immune response against an antigenic peptide, said method comprising administering to said mammal a composition comprising (a) an amount of a noncovalent complex of a mammalian stress protein and an antigenic peptide sufficient to elicit in said mammal an immune response against said antigenic peptide, which complex is the product of complexing said mammalian stress protein and said antigenic peptide in vitro;
- and (b) a pharmaceutically acceptable carrier.
A composition for inducing a therapeutic immune response in a subject, comprising:
- a) a target antigen;
- and
- b) a heat shock protein;
- wherein the target antigen and the heat shock protein are combined in vitro under conditions wherein binding of target antigen to heat shock protein occurs to form a target antigen/heat shock protein complex;
- and
- wherein the administration of the target antigen/heat shock protein complex to the subject induces an immune response comprising a cytotoxic cellular component.
A method of inducing a therapeutic immune response in a subject in need of such treatment, comprising administering to the subject a therapeutically effective amount of a composition comprising:
- a) a target antigen;
- and
- b) a heat shock protein;
- wherein the target antigen and heat shock protein are combined in vitro under conditions wherein binding of target antigen to heat shock protein occurs to form a target antigen/heat shock protein complex;
- and
- wherein the administration of the target antigen/heat shock protein complex to the subject induces an immune response comprising a cytotoxic cellular component.
Dependencies are inferred from the claim text.