Methods for producing an immune response to tuberculosis
Inventors
Lewinsohn, David • Lewinsohn, Deborah
Assignees
US Department of Veterans Affairs
Publication Number
US-7842299-B2
Publication Date
2010-11-30
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
Methods for producing an immune response to Mycobacterium tuberculosis (Mtb) are disclosed herein. The invention includes methods for treating an Mtb infection or preventing an Mtb infection in a subject, where the Mtb infection can be latent or active. The disclosed methods involve administering to the subject a therapeutically effective amount of a polypeptide, or a polynucleotide encoding the polypeptide, wherein the polypeptide comprises at least one of the amino acid sequences set forth as SEQ ID NOs: 1-12, or peptides thereof that specifically bind major histocompatibility complex (MHC) class I.
The invention addresses the problem that current Mycobacterial vaccines, such as BCG for M. tuberculosis, are inadequate or unavailable. Tuberculosis remains a major health risk globally, particularly among immunocompromised patients, with an increase in multidrug resistant strains and pathogenic mycobacterial strains. There are no effective vaccines or therapeutic strategies that induce a protective immune response, especially a CD8+ T cell response, to Mtb. Mycobacterium tuberculosis-specific CD4+ and CD8+ T cells are critical for controlling infection, and a need remains for agents that can induce such immune responses for treatment and protection.
The invention further discloses isolated polypeptides comprising nine to twenty consecutive amino acids of the defined Mtb sequences that specifically bind MHC class I. Pharmaceutical compositions comprising these polypeptides, nucleic acids encoding them, and host cells containing such nucleic acids are also disclosed. The methods can induce protective immune responses, prevent infection, or treat infection by Mtb. The compositions can be administered with adjuvants or carriers to enhance the immune response.
Claims Coverage
The patent claims cover methods for producing an immune response to Mycobacterium tuberculosis and for treating Mtb infection using isolated polypeptides comprising specific amino acid sequences, primarily SEQ ID NO: 10. There are fourteen claims with independent claims directed to these methods.
Method for inducing immune response with an isolated polypeptide
Administering to a subject a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 10 to induce an immune response to Mycobacterium tuberculosis.
Method for treating infection using an isolated polypeptide
Administering to a subject infected with Mycobacterium tuberculosis a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 10 to treat the infection.
Use of polypeptides covalently linked to a carrier
The isolated polypeptide can be covalently linked to a carrier to enhance immunogenicity during administration.
Use of adjuvants to enhance immune response
Administering a therapeutically effective amount of an adjuvant in combination with the isolated polypeptide to enhance the immune response.
Application to subjects at risk or infected with Mtb
The methods apply to subjects who are infected, at risk for infection, or have latent infection with Mycobacterium tuberculosis.
Isolated polypeptide consisting of SEQ ID NO: 10
The isolated polypeptide used in the methods can consist solely of the amino acid sequence set forth as SEQ ID NO: 10.
The claims define methods of inducing an immune response or treating tuberculosis by administering isolated polypeptides with the sequence of SEQ ID NO: 10, optionally linked to carriers and combined with adjuvants, applicable to both infected and at-risk subjects.
Stated Advantages
The methods induce a protective immune response against Mycobacterium tuberculosis.
The compositions can prevent infection or progression of latent infection to active tuberculosis.
The invention provides effective strategies to induce CD8+ T cell responses, which were not effectively induced by prior vaccines.
Documented Applications
Producing an immune response to Mycobacterium tuberculosis in a subject.
Treating a subject infected with Mycobacterium tuberculosis, including latent and active infections.
Preventing infection with Mycobacterium tuberculosis in subjects at risk of exposure.
Administering antigen presenting cells pulsed with Mtb polypeptides to induce immune responses.
Use in animal models, such as mice and guinea pigs, to prevent or treat tuberculosis and measure efficacy by bacterial counts and immunological markers.
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