US2005232897A1PendingUtilityA1
Mucosal cytotoxic T lymphocyte responses
Est. expirySep 11, 2017(expired)· nominal 20-yr term from priority
A61K 39/12A61K 2039/6037C07K 14/005C12N 2740/16134A61K 2039/55522A61K 39/21A61K 2039/55538A61K 2039/541A61K 2039/545C12N 2740/16122A61K 2039/55544Y10S530/826C12N 2710/24143A61K 2039/5256A61K 2039/55566
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Claims
Abstract
The invention provides methods for induction of an antigen-specific, mucosal cytotoxic T lymphocyte response useful in preventing and treating infections with pathogens that gain entry via a mucosal surface.
Claims
exact text as granted — not AI-modified1 . A method for inducing a protective mucosal cytotoxic T lymphocyte (CTL) response in a mammalian subject comprising contacting a mucosal tissue of the subject with a composition comprising a purified soluble antigen.
2 . The method of claim 1 , wherein the soluble antigen is an antigenic peptide.
3 . The method of claim 1 , wherein said composition further comprises an adjuvant.
4 . The method of claim 3 , wherein the adjuvant is selected from cholera toxin (CT), mutant cholera toxin (MCT), or mutant- E. coli heat labile enterotoxin (MLT).
5 . The method of claim 1 , further comprising administering a purified cytokine to the subject.
6 . The method of claim 1 , wherein the cytokine is contacted with a mucosal surface of the subject.
7 . The method of claim 5 , wherein the purified cytokine is selected from granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12) or tumor necrosis factor a (TNFa).
8 . The method of claim 1 , further comprising administering purified interferon-γ to the subject.
9 . The method of claim 8 , wherein the purified interferon-γ is contacted with a mucosal surface of the subject.
10 . The method of claim 5 , further comprising administering purified interferon-γ to the subject.
11 . The method of claim 10 , wherein the purified interferon-γ is contacted with a mucosal surface of the subject.
12 . The method of claim 1 , wherein said composition further comprises a purified cytokine selected from granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12) or tumor necrosis factor.
13 . The method of claim 1 , wherein said composition further comprises purified interferon-γ.
14 . The method of claim 12 , wherein said composition further comprises purified interferon-γ.
15 . The method of claim 1 , wherein the antigen is a peptide derived from a pathogenic virus.
16 . The method of claim 15 , wherein the pathogenic virus is HIV-1.
17 . The method of claim 15 , wherein the pathogenic virus is influenza virus.
18 . The method of claim 15 , wherein the pathogenic virus is rotavirus.
19 . The method of claim 1 , wherein the antigen is a peptide derived from a pathogenic bacterium or protozoan.
20 . The method of claim 1 , wherein the antigen is a tumor-associated peptide.
21 . The method of claim 1 , wherein the antigen is a peptide comprising an HIV-1 cluster peptide vaccine construct (CLUVAC) selected from the group consisting of:
(SEQ ID NO:1)
EQMHEDIISLWDQSLKPCVKRIQRGPGRAFVTIGK,
(SEQ ID NO:2)
KQIINMWQEVGKAMYAPPISGQIRRIQRGPGRAFVTIGK,
(SEQ ID NO:3)
RDNWRSELYKYKVVKIEPLGVAPTRIQRGPGRAFVTIGK,
(SEQ ID NO:4)
AVAEGTDRVIEVVQGAYRAIRHIPRRIRQGLERRIQRGPGRAFVTIGK,
(SEQ ID NO:5)
DRVIEVVQGAYRAIRHIPRRIRQGLERRIQRGPGRAFVTIGK,
(SEQ ID NO:6)
DRVIEVVQGAYRAIRRIQRGPGRAFVTIGK,
(SEQ ID NO:7)
AQGAYRAIRHIPRRIRRIQRGPGRAFVTIGK,
(SEQ ID NO:8)
EQMHEDIISLWDQSLKPCVKRIHIGPGRAFYTTKN,
(SEQ ID NO:9)
KQIINMWQEVGKAMYAPPISGQIRRIHIGPGRAFYTTKN,
(SEQ ID NO:10)
RDNWRSELYKYKVVKIEPLGVAPTRIHIGPGRAFYTTKN,
SEQ ID NO:11)
AVAEGTDRVIEVVQGAYRAIRHIPRRIRQGLERRIHIGPGRAFYTTKN,
(SEQ ID NO:12)
DRVIEVVQGAYRAIRHIPRRIRQGLERRIHIGPGRAFYTTKN,
(SEQ ID NO:13)
DRVIEVVQGAYRAIRRIHIGPGRAFYTTKN
and
(SEQ ID NO:14)
AQGAYRAIRHIPRRIRRIHIGPGRAFYTTKN.
22 . (canceled)
23 . The method of claim 21 , wherein the HIV-1 CLUVAC is HIV-1 CLUVAC PCLUS3-18MN (SEQ ID NO:9).
24 . The method of claim 21 , wherein the HIV-1 CLUVAC is HIV-1 CLUVAC PCLUS 6.1-18MN (SEQ ID NO:12).
25 . A method for inducing a protective mucosal CTL response in a subject, comprising contacting a mucosal tissue of the subject with a composition comprising a soluble antigen, wherein said composition does not comprise an adjuvant.
26 . The method of claim 25 , further comprising administering a purified cytokine to the subject.
27 . The method of claim 25 , wherein the cytokine is contacted with a mucosal surface of the subject.
28 . The method of claim 27 , wherein the purified cytokine is selected from granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12) or tumor necrosis factor a (TNFa).
29 . The method of claim 25 , further comprising administering purified interferon-γ to the subject.
30 . The method of claim 29 , wherein the purified interferon-γ is contacted with a mucosal surface of the subject.
31 . The method of claim 26 , further comprising administering purified interferon-γ to the subject.
32 . The method of claim 31 , wherein the purified interferon-γ is contacted with a mucosal surface of the subject.
33 . The method of claim 25 , wherein said composition further comprises a purified cytokine selected from granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12) or tumor necrosis factor.
34 . The method of claim 25 , wherein said composition further comprises purified interferon-γ.
35 . The method of claim 33 , wherein said composition further comprises purified interferon-γ.
36 . The method of claim 25 , wherein the antigen is a peptide derived from a pathogenic virus.
37 . The method of claim 36 , wherein the pathogenic virus is HIV-1.
38 . The method of claim 36 , wherein the pathogenic virus is influenza virus.
39 . The method of claim 36 , wherein the pathogenic virus is rotavirus.
40 . The method of claim 25 , wherein the antigen is a peptide derived from a pathogenic bacterium or protozoan.
41 . The method of claim 25 , wherein the antigen is a tumor-associated peptide.
42 . The method of claim 25 , wherein the antigen is a peptide comprising an HIV-1 cluster peptide vaccine construct (CLUVAC) selected from the group consisting of:
(SEQ ID NO:1)
EQMHEDIISLWDQSLKPCVKRIQRGPGRAFVTIGK,
(SEQ ID NO:2)
KQIINMWQEVGKAMYAPPISGQIRRIQRGPGRAFVTIGK,
(SEQ ID NO:3)
RDNWRSELYKYKVVKIEPLGVAPTRIQRGPGRAFVTIGK,
(SEQ ID NO:4)
AVAEGTDRVIEVVQGAYRAIRHIPRRIRQGLERRIQRGPGRAFVTIGK,
(SEQ ID NO:5)
DRVIEVVQGAYRAIRHIPRRIRQGLERRIQRGPGRAFVTIGK,
(SEQ ID NO:6)
DRVIEVVQGAYRAIRRIQRGPGRAFVTIGK,
(SEQ ID NO:7)
AQGAYRAIRHIPRRIRRIQRGPGRAFVTIGK,
(SEQ ID NO:8)
EQMHEDIISLWDQSLKPCVKRIHIGPGRAFYTTKN,
(SEQ ID NO:9)
KQIINMWQEVGKAMYAPPISGQIRRIHIGPGRAFYTTKN,
(SEQ ID NO:10)
RDNWRSELYKYKVVKIEPLGVAPTRIHIGPGRAFYTTKN,
(SEQ ID NO:11)
AVAEGTDRVIEVVQGAYRAIRHIPRRIRQGLERRIHIGPGRAFYTTKN,
(SEQ ID NO:12)
DRVIEVVQGAYRAIRHIPRRIRQGLERRIHIGPGRAFYTTKN,
(SEQ ID NO:13)
DRVIEVVQGAYRAIRRIHIGPGRAFYTTKN
and
(SEQ ID NO:14)
AQGAYRAIRHIPRRIRRIHIGPGRAFYTTKN.
43 . (canceled)
44 . The method of claim 42 , wherein the HIV-1 CLUVAC is HIV-1 CLUVAC PCLUS3-18MN (SEQ ID NO:9).
45 . The method of claim 42 , wherein the HIV-1 CLUVAC is HIV-1 CLUVAC PCLUS 6.1-18MN (SEQ ID NO:12).
46 . An immunogenic composition for inducing a protective mucosal CTL response in a subject and adapted for intrarectal administration comprising a purified soluble antigen formulated for intrarectal delivery to the rectum, colon, sigmoid colon, or distal colon.
47 . The immunogenic composition of claim 46 , which comprises a rectal enema, foam, suppository, or topical gel.
48 . The immunogenic composition of claim 46 , further comprising a base, carrier, or absorption-promoting agent adapted for intrarectal delivery.
49 . The immunogenic composition of claim 48 , which includes a rectal emulsion or gel preparation.
50 . The immunogenic composition of claim 48 , wherein the soluble antigen is admixed with a homogenous gel carrier.
51 . The immunogenic composition of claim 48 , wherein the homogenous gel carrier is a polyoxyethylene gel.
52 . The immunogenic composition of claim 48 , wherein the soluble antigen is admixed with a rectally-compatible foam.
53 . The immunogenic composition of claim 48 , wherein the soluble antigen is formulated in a suppository.
54 . The immunogenic composition of claim 53 , wherein the suppository is comprised of a base selected from a polyethyleneglycol, witepsol H15, witepsol W35, witepsol E85, propyleneglycol dicaprylate (Sefsol 228), Miglyol810, hydroxypropylcellulose-H (HPC), or carbopol-934P (CP).
55 . The immunogenic composition of claim 53 , comprising at least two base materials.
56 . The immunogenic composition of claim 46 , including a stabilizing agent to minimize intrarectal degradation of the soluble antigen.
57 . The immunogenic composition of claim 46 , including an absorption-promoting agent.
58 . The immunogenic composition of claim 57 , wherein the absorption-promoting agent is selected from a surfactant, mixed micelle, enamines, nitric oxide donor, sodium salicylate, glycerol ester of acetoacetic acid, clyclodextrin or beta-cyclodextrin derivative, or medium-chain fatty acid.
59 . The immunogenic composition of claim 46 , further comprising an adjuvant.
60 . The immunogenic composition of claim 59 , wherein the adjuvant is selected from cholera toxin (CT), mutant cholera toxin (MCT), mutant- E. coli heat labile enterotoxin, o(Original) r pertussis toxin.
61 . The immunogenic composition of claim 59 , wherein the adjuvant is conjugated to a mucosal tissue or T cell binding agent.
62 . The immunogenic composition of claim 61 , wherein the mucosal tissue or T cell binding agent is selected from protein A, an antibody that binds a mucosal tissue- or T-cell-specific protein, or a ligand or peptide that binds a mucosal tissue- or T-cell-specific protein.
63 . The immunogenic composition of claim 59 , wherein the adjuvant comprises a recombinant cholera toxin (CT) having a B chain of CT substituted by protein A conjugated to a CT A chain to eliminate toxicity and enhance mucosal tissue binding mediated by protein A.
64 . The immunogenic composition of claim 59 , wherein the adjuvant is conjugated to a protein or peptide that binds specifically to T cells.
65 . The immunogenic composition of claim 64 , wherein the protein or peptide binds to CD4 or CD8.
66 . The immunogenic composition of claim 66 , wherein the protein or peptide is an HIV V3 loop or T cell-binding peptide fragment thereof.
67 . The immunogenic composition of claim 59 , further comprising purified IL-12.
68 . The immunogenic composition of claim 59 , further comprising purified interferon-γ.
69 . The immunogenic composition of claim 68 , further comprising purified IL-12.Cited by (0)
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