Recombinant mycobacterium avium subsp. paratuberculosis proteins induce immunity and protect against infection
Inventors
Stabel, Judith R. • Bannantine, John P.
Assignees
US Department of Agriculture USDA
Publication Number
US-9175049-B2
Publication Date
2015-11-03
Expiration Date
2033-09-26
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Abstract
Compositions of immunogenic proteins of Mycobacterium avium subspecies paratuberculosis (MAP) are effective for stimulating a protective immune response in animals against MAP. Combinations of MAP1087 with two or more of MAP1204, MAP1272c and MAP2077c are effective for stimulating a protective immune response in animals against MAP and can be administered as vaccines against paratuberculosis (Johne's disease). Induction of the immune response significantly reduces or eliminates colonization of the animal by MAP, and consequently reduces or eliminates the symptoms of clinical disease in animals infected with MAP and reduces or eliminates fecal shedding of MAP. Vaccination with the compositions provides protection against clinical disease and reduces transmission of MAP infection within a herd.
Core Innovation
The invention relates to compositions of immunogenic proteins of Mycobacterium avium subspecies paratuberculosis (MAP) effective for stimulating a protective immune response in animals against MAP. The compositions include MAP1087 combined with at least two of MAP1204, MAP1272c, and MAP2077c and can be administered as vaccines against paratuberculosis (Johne's disease). Vaccination with these compositions significantly reduces or eliminates colonization of the animal by MAP, the symptoms of clinical disease, and fecal shedding of MAP, thereby providing protection and reducing transmission within a herd.
The problem addressed by the invention is that existing whole cell vaccines, such as heat-killed preparations approved in the US, have drawbacks including causing adverse reactions like severe inflammation and granuloma formation at injection sites, and interfering with diagnostic tests for bovine tuberculosis and MAP infections. While previous subunit vaccines have induced immune responses and provided some protection, there remains a need for improved vaccines that effectively protect animals against paratuberculosis without these limitations.
The invention provides novel vaccines comprising isolated and recombinant MAP proteins MAP1087, MAP1204, MAP1272c, and MAP2077c, alone or in combinations, which elicit protective immune responses mediated by both humoral and cellular immunity. These compositions provide effective protection by reducing MAP colonization and clinical disease, with demonstrated immunogenicity and efficacy in animal models, including mice challenged with live MAP. The vaccines may be formulated with pharmaceutically acceptable carriers and adjuvants, and are suitable for administration to various susceptible animals such as ruminants.
Claims Coverage
The patent includes eight independent claims defining compositions and methods related to immunogenic proteins from Mycobacterium avium subspecies paratuberculosis and their use.
Composition comprising specific MAP immunogenic proteins and carriers
A composition comprising isolated and purified immunogenic proteins MAP1087 and at least two of MAP1204, MAP1272c, and MAP2077c, provided in an amount effective to stimulate an immune response against MAP, combined with a pharmaceutically acceptable carrier selected from physiological saline, phosphate buffered saline, mineral oil, vegetable oil, aqueous carboxymethyl cellulose, and polyvinylpyrrolidone.
Immunogenic composition comprising fusion proteins MAP/MBP
An immunogenic composition comprising fusion proteins MAP1087/MBP and at least two of the fusion proteins MAP1204/MBP, MAP1272c/MBP, and MAP2077c/MBP, where each fusion protein corresponds to specified SEQ ID NOs, effectively stimulating immune response against MAP.
Method for reducing MAP colonization by administering immunogenic proteins
A method for reducing MAP colonization in an animal by administering an immunologically effective dose of isolated and purified MAP1087 and at least two of MAP1204, MAP1272c, and MAP2077c in a pharmaceutically acceptable carrier, wherein the dose elicits protective immune response sufficient to protect the animal from infection.
Method for reducing MAP colonization by administering fusion protein compositions
A method for reducing MAP colonization involving administering an immunologically effective dose of fusion protein immunogenic compositions comprising MAP1087/MBP and at least two of MAP1204/MBP, MAP1272c/MBP, and MAP2077c/MBP that induce immune protection against MAP infection.
Method of generating a Th1 immune response against MAP using isolated proteins
A method of generating a Th1 immune response in an animal by administering a composition comprising isolated and purified MAP1087 and at least two of MAP1204, MAP1272c, and MAP2077c in a pharmaceutically acceptable carrier, in an amount sufficient to generate the Th1 response against MAP.
Method of generating a Th1 immune response using fusion proteins
A method of generating a Th1 immune response by administering a composition comprising fusion proteins MAP1087/MBP and at least two of MAP1204/MBP, MAP1272c/MBP, and MAP2077c/MBP in an amount sufficient to generate the Th1 immune response in animals against MAP.
The independent claims cover compositions of specific isolated MAP immunogenic proteins or their fusion protein forms in pharmaceutically acceptable carriers, and methods of administering these compositions to animals to elicit protective immune responses and reduce colonization and infection by MAP, including inducing Th1-mediated immunity. The claims include variations of protein combinations and compositions with or without adjuvants, and specify effective dosage ranges.
Stated Advantages
The vaccine compositions significantly reduce or eliminate colonization of the animal by MAP.
Vaccination reduces or eliminates symptoms of clinical paratuberculosis disease in infected animals.
Vaccination reduces or eliminates fecal shedding of MAP, thereby reducing transmission within herds.
The vaccines induce both humoral and cell-mediated immune responses, including Th1-type immunity.
Recombinant protein vaccines provide advantages over whole cell vaccines by reducing adverse reactions and diagnostic interference.
Documented Applications
Use as vaccines to induce immunity and protect animals against infection by Mycobacterium avium subspecies paratuberculosis (MAP).
Administration to ruminant animals including bovine (cattle), bison, caprine (goats), ovine (sheep), deer, elk, and other susceptible wildlife species for prevention of paratuberculosis (Johne's disease).
Formulation of vaccines for treatment of neonatal and adult animals to reduce MAP colonization, disease symptoms, and transmission within herds.
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