Methods and compositions for treating P. acnes
Inventors
Gallo, Richard L. • Huang, Chun-Ming
Assignees
Office of General Counsel of VA • University of California San Diego UCSD
Publication Number
US-9340769-B2
Publication Date
2016-05-17
Expiration Date
2029-12-03
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Abstract
The disclosure provides an antigenic composition useful for immunization against P. acnes, K. pneumoniae, S. aureus, or Streptococcus pyogenes. The disclosure provides a method for producing a vaccine for preventing infection and screening agents useful for preventing infection.
Core Innovation
The invention provides antigenic compositions and methods for treating or preventing infection by Propionibacterium acnes (P. acnes). It includes vaccines comprising P. acnes CAMP factor, methods for producing these vaccines, and use of antibodies against CAMP factor. The compositions also involve ASMase inhibitors, including small molecules or antibodies, alone or in combination with CAMP factor vaccines or antibodies. This approach aims to suppress P. acnes-induced diseases and inflammation in humans and animals.
The problem addressed arises from P. acnes being an opportunistic pathogen involved in various infections and inflammatory conditions, notably acne vulgaris, which affects a large portion of the population. Existing treatments like antibiotics are non-specific, short-lasting, and generally applied after lesion development, often leading to resistance and relapse. There is a lack of vaccines that specifically target P. acnes to prevent infection and associated inflammation without disturbing normal flora or hormonal balance.
The disclosure identifies secretory virulence factors of P. acnes, including CAMP factor, lipase, and sialidase, that are highly expressed under anaerobic conditions typical of acne lesions. It demonstrates that P. acnes CAMP factor acts synergistically with host acid sphingomyelinase (ASMase), enhancing bacterial pathogenicity and inflammation. Vaccination with CAMP factor or sialidase antigens induces protective immunity, reducing inflammation and bacterial virulence. The compositions encompass vaccines delivered by attenuated bacterial or viral vectors, recombinant proteins, killed or disrupted bacteria, and plant-based expression systems. The combination of CAMP factor vaccination with ASMase inhibition exhibits synergistic effects in preventing P. acnes-induced inflammation.
Claims Coverage
The patent includes multiple independent claims covering immunogenic compositions and methods using attenuated bacterial vectors expressing specific P. acnes polypeptides or peptides, as well as methods of inducing protective immunity against P. acnes.
Immunogenic composition with attenuated bacterial vectors expressing specific P. acnes polypeptides or peptides
An immunogenic composition comprising attenuated bacterial vectors that express polypeptides comprising SEQ ID NO:9 or 11 and/or peptides consisting of SEQ ID NO:2 or 3; these compositions induce an immunoprotective response against P. acnes.
Use of specific attenuated bacterial vectors as delivery vehicles
Employing attenuated bacterial vectors such as Escherichia coli and other bacteria selected from a defined group to express P. acnes antigens (SEQ ID NO:7, 9 or 11, or peptides SEQ ID NO:2 or 3) for immunization purposes.
Method of inducing protective immunity via administration of immunogenic compositions
Administering the immunogenic compositions containing attenuated bacterial vectors expressing the specific P. acnes polypeptides or peptides to a subject, sufficient to induce protective immunity against P. acnes.
Recombinant attenuated bacterial vectors encoding P. acnes antigenic polypeptides or peptides
Recombinant attenuated bacterial vectors comprising polynucleotides encoding antigenic polypeptides comprising SEQ ID NO:9 or 11, or antigenic peptides consisting of SEQ ID NO:2 or 3 for induction of immunity against P. acnes.
Immunoprotective compositions with vectors linked to transcriptional control sequences
Immunoprotective compositions comprising attenuated bacterial vectors expressing antigens consisting of polypeptides or peptides (SEQ ID NO:7, 9 or 11 and SEQ ID NO:2 or 3) linked to transcriptional promoters and termination signals to induce immunoprotection against P. acnes.
Composition providing cross-protection against related pathogens
The composition also conveys protective immunity against infections by Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes, in addition to P. acnes.
The claims broadly cover immunogenic compositions comprising attenuated bacterial vectors expressing defined P. acnes antigens (notably sequences SEQ ID NO:7, 9, 11, and peptides SEQ ID NO:2 or 3), methods of inducing immunity in subjects via administration of such compositions or vectors, and recombinant vectors encoding these antigens. The coverage includes use of various bacterial vectors, compositions with linked genetic elements, and compositions conferring cross-protection against certain other bacteria.
Stated Advantages
Vaccines selectively suppress P. acnes-induced inflammation without disrupting hormonal balance or skin resident flora.
Compositions provide protective immunity against P. acnes infections and associated inflammatory diseases.
Combination of CAMP factor vaccination and ASMase inhibition synergistically reduces P. acnes-induced inflammation and skin lesions.
Passive immunization with antibodies against CAMP factor provides immediate therapeutic benefits, minimizing impact on beneficial microbes and lowering risks of drug resistance.
Immunogenic compositions can be delivered using multiple platforms including attenuated bacterial or viral vectors and plant-based systems, offering versatile vaccination strategies.
Documented Applications
Prevention and treatment of P. acnes-associated diseases including acne vulgaris, endocarditis, endophthalmitis, osteomyelitis, infections related to implanted biomaterials, joint and nervous system infections, and cranial neurosurgery infections.
Use of immunogenic compositions and vaccines to induce protective immunity against P. acnes infection to reduce inflammation and bacterial colonization.
Use of combination therapy with CAMP factor-based vaccines and ASMase inhibitors/antibodies to synergistically suppress P. acnes-induced inflammation and skin lesions.
Applications include immunization of humans and animals via various routes (e.g., intranasal, subcutaneous, oral) to prevent P. acnes infection.
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