Methods for producing an immune response to tuberculosis
Inventors
Lewinsohn, David • Lewinsohn, Deborah
Assignees
US Department of Veterans Affairs
Publication Number
US-8440206-B2
Publication Date
2013-05-14
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. The methods encompass administering therapeutically effective amounts of isolated polypeptides or polynucleotides encoding polypeptides, comprising specific amino acid sequences of Mtb proteins, or fragments thereof, capable of specifically binding major histocompatibility complex (MHC) class I molecules. These immune responses can be used for preventing an infection with Mtb, treating active or latent Mtb infections, or inducing a protective immune state in a subject.
The problem addressed arises from the global burden of tuberculosis, with approximately one-third of the world's population harboring Mtb bacteria and being at risk for developing tuberculosis (TB). Existing vaccines, such as BCG, are inadequate, and no current vaccines or therapeutic strategies effectively induce a CD8+ T cell immune response to Mtb. Given the critical roles of Mtb-specific CD4+ and CD8+ T cells in controlling infection and the emergence of multidrug-resistant strains, there is a pressing need for agents that can generate effective immune responses to Mtb for treatment and protection.
Claims Coverage
The patent includes one independent claim covering methods for inducing immune responses and treating Mtb infection using an isolated polypeptide.
Use of polypeptide with amino acid sequence SEQ ID NO: 7 to induce immune response
A method for producing an immune response to Mycobacterium tuberculosis in a subject by administering a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 7, thereby inducing an immune response to Mycobacterium tuberculosis.
Use of polypeptide with amino acid sequence SEQ ID NO: 7 for treatment of tuberculosis
A method for treating a subject infected with Mycobacterium tuberculosis by administering a therapeutically effective amount of an isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO: 7, thereby treating the subject infected with Mycobacterium tuberculosis.
The claims focus on methods that administer isolated polypeptides consisting of or comprising the amino acid sequence SEQ ID NO: 7, alone or in pharmaceutical compositions, optionally with adjuvants or linked to carriers, for inducing immune responses against Mtb or treating infected or at-risk subjects.
Stated Advantages
The invention provides polypeptides that induce protective immune responses against Mycobacterium tuberculosis, potentially overcoming the inadequacies of current vaccines.
The disclosed methods can prevent infection, treat active or latent tuberculosis, and induce a measurable T cell immune response, including CD8+ T cell responses critical for effective control.
Use of isolated Mtb polypeptides or polynucleotides allows targeted immunogenic stimulation, which may result in higher frequency and immunodominance of CD8+ T cells recognizing Mtb antigens.
Documented Applications
Preventing infection with Mycobacterium tuberculosis in subjects at risk, including those exposed or with latent infection.
Treating active or latent tuberculosis infection by inducing or enhancing immune responses in infected subjects.
Use in pharmaceutical compositions for immunization to produce protective immune responses against tuberculosis.
Ex vivo and in vivo activation of antigen presenting cells, such as dendritic cells, pulsed with Mtb polypeptides for adoptive immunotherapy.
Screening of T cell clones and subjects for immunodominant Mtb-specific CD8+ T cell epitopes for vaccine development.
Use of viral or microbial vectors to express Mtb polypeptides in hosts for immunization.
Testing and evaluation of immunogenicity and protection in animal models including mice and guinea pigs challenged with Mtb.
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