Use of glycosylceramides as adjuvants for vaccines against infections and cancer
AssigneeNew York University
InventorsMoriya Tsuji, Gloria Gonzalez-Aseguinolaza, Yasuhiko Koezuka
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Abstract
The present invention relates to methods and compositions for augmenting an immunogenicity of an antigen in a mammal, comprising administering said antigen together with an adjuvant composition that includes glycosylceramide, preferably α-galactosylceramide (α-GalCer). According to the present invention, the use of glycosylceramide as an adjuvant is attributed at least in part to the enhancement and/or extension of antigen-specific Th1-type responses, in particular, CD8+ T cell responses. The methods and compositions of the present invention can be useful for prophylaxis and treatment of various infectious and neoplastic diseases.
Claims64
A method for augmenting the immunogenicity of an antigen in a mammal, comprising immunizing the mammal with said antigen and conjointly with an adjuvant comprising a glycosylceramide of the general Formula 1:
- 17
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5.
A method for enhancing or extending the duration of antigen-specific Th1-type immune responses in a mammal comprising conjointly administering to said mammal (i) an antigen and (ii) an adjuvant comprising a glycosylceramide of the general Formula 1:
- 18
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5.
A method for treating a disease in a mammal comprising conjointly administering to said mammal an antigen and an adjuvant comprising a glycosylceramide of the general Formula 1:
- 19
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5.
A pharmaceutical composition comprising an immunogenically effective amount of an adjuvant comprising a glycosylceramide of the general Formula 1:
- 20
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5.
A vaccine composition comprising an immunogenically effective amount of an antigen and an immunogenically effective amount of an adjuvant comprising a glycosylceramide of the general Formula 1:
- 21
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5.
A method for conferring immunity against the sporozoite stage of malaria to a susceptible mammalian host comprising conjointly administering to said host
- (i) at least one malaria-specific antigen selected from the group consisting of sporozoite surface antigens in a first amount, and
- (ii) α-galactosylcaramide (α-GalCer) as an immune adjuvant in a second amount;
- said first and second amounts being effective in combination to enhance or prolong the immune response mounted against said antigen by the host compared to the immune response that the host could have mounted upon the administration of said first amount of said antigen without the conjoint administration of said adjuvant.
A method for enhancing a T cell response to an HIV antigen in a susceptible mammalian host comprising conjointly administering to said host:
- (i) at least one HIV-specific antigen selected from the group consisting of Gag, Tat, Pol, Env, Nef, gp160, p18, and gp120 in a first amount, and
- (ii) α-galactosylcaramide (α-GalCer) as an immune adjuvant in a second amount;
- said first and second amounts being effective in combination to enhance said T cell response mounted against said antigen by the host compared to the immune response that the host could have mounted upon the administration of said first amount of said antigen without the conjoint administration of said adjuvant.
A method for preparing a vaccine composition comprising at least one antigen and an adjuvant comprising a glycosylceramide of the general Formula 1:
- 22
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5, said method comprising admixing the adjuvant and the antigen.
A kit for the preparation of a pharmaceutical or vaccine composition comprising at least one antigen and an adjuvant, wherein the adjuvant comprises a glycosylceramide of the general Formula 1:
- 23
- wherein R1, R2 and R5 represent H or a specific monosaccharide;
- R3 and R6 represent H or OH, respectively;
- R4 represents H, OH or a specific monosaccharide;
- X denotes an integer from 1 to 23;
- R7 represents any one of the following groups (a)-(g):
- (a) —(CH2)11—CH3, (b) —(CH2)12—CH3, (c) —(CH2)13—CH3, (d) —(CH2)9—CH(CH3)2, (e) —(CH2)10—CH(CH3)2, (f) —(CH2)11—CH(CH3)2, (g) —(CH2)11—CH(CH3)—C2H5, said kit comprising the antigen in a first container, and the adjuvant in a second container, and optionally instructions for admixing the antigen and the adjuvant and/or for administration of the composition;
- and wherein optionally the containers are in a package.
Dependencies are inferred from the claim text.