Methods for producing an immune response to tuberculosis
Inventors
Lewinsohn, David • Lewinsohn, Deborah
Assignees
US Department of Veterans Affairs
Publication Number
US-8101192-B2
Publication Date
2012-01-24
Expiration Date
2027-03-14
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Abstract
Methods for producing an immune response to Mycobacterium tuberculosis (Mtb) are disclosed herein. In several examples, the immune response is a protective immune response. In additional embodiments, methods are disclosed for preventing an infection with Mtb, or treating an infection with Mtb. Pharmaceutical compositions for the prevention and/or treatment of tuberculosis are also disclosed.
Core Innovation
The invention discloses methods for producing an immune response to Mycobacterium tuberculosis (Mtb), including protective immune responses, as well as methods for preventing and treating Mtb infections, whether latent or active. These methods involve administering to a subject therapeutically effective amounts of specific Mtb polypeptides or polynucleotides encoding them, where the polypeptides comprise defined amino acid sequences set forth as SEQ ID NOs: 1 through 12 or fragments thereof that specifically bind to major histocompatibility complex (MHC) class I molecules.
The background addresses the problem that tuberculosis remains a major global health threat, with one third of the world’s population harboring Mtb and the incidence increasing among immunocompromised individuals, including those with HIV/AIDS. Current vaccines like BCG are inadequate, and there are no therapeutic strategies that effectively induce cellular immune responses, particularly CD8+ T cell responses, which are critical for controlling Mtb infection. There is an unmet need for agents capable of inducing effective immune responses to Mtb for prevention and treatment.
The invention overcomes the inadequacy of existing vaccines and therapeutic approaches by identifying and utilizing specific immunogenic Mtb polypeptides and epitopes that elicit strong CD8+ T cell responses. These polypeptides include full-length proteins and isolated peptides of nine to twenty amino acids that bind MHC class I and stimulate cytotoxic T lymphocytes. The disclosed pharmaceutical compositions and methods induce immune responses that can prevent infection, treat active disease, or control latent infection.
Claims Coverage
The patent presents one independent claim covering methods of inducing an immune response and treating infection with Mycobacterium tuberculosis using a specific isolated polypeptide.
Use of a defined isolated polypeptide to induce immune response
Administering to a subject a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 8 to produce an immune response to Mycobacterium tuberculosis.
Treatment of Mtb infection with a specified isolated polypeptide
Administering a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 8 to treat a subject infected with Mycobacterium tuberculosis.
Inclusion of pharmaceutical compositions containing the specified polypeptide
Use of pharmaceutical compositions comprising the isolated polypeptide of SEQ ID NO: 8 for inducing immune responses or treating Mtb infection.
Optional use of adjuvants in methods employing the polypeptide of SEQ ID NO: 8
Co-administering a therapeutically effective amount of an adjuvant together with the isolated polypeptide to enhance the immune response.
Administration to different subject groups
Methods applicable to subjects infected, at risk of infection, or having latent infection with Mycobacterium tuberculosis.
Use of covalently linked polypeptide-carrier
The isolated polypeptide of SEQ ID NO: 8 may be covalently linked to a carrier protein in the methods of immune induction or treatment.
The claims define methods for inducing an immune response and treating tuberculosis using a therapeutically effective amount of a specific Mtb polypeptide (SEQ ID NO: 8), optionally with adjuvants or linked carriers, applicable to various subject groups including infected and at-risk individuals.
Stated Advantages
The disclosed methods provide agents capable of producing protective immune responses specifically targeting Mtb.
The use of defined Mtb polypeptides enhances induction of CD8+ T cell-mediated immunity, which is critical for controlling Mtb infection.
The methods address the deficiency of current vaccines and therapies by effectively inducing protective cellular immunity to Mtb.
Documented Applications
Preventing infection with Mycobacterium tuberculosis in subjects at risk of exposure.
Treating subjects infected with Mycobacterium tuberculosis, including those with latent or active tuberculosis.
Administration of Mtb polypeptides, polynucleotides, or antigen-presenting cells pulsed with such polypeptides to induce immune responses.
Use in animal models such as mice and guinea pigs to prevent or treat Mtb infection and assess immune responses and pathology.
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