Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1994-07-11
1997-12-09
Sidberry, Hazel F.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
4242361, 4242531, 4242031, 424 933, A61K 39102, A61K 3910, A61K 39116, A61K 3902
Patent
active
056957696
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is generally in the field of veterinary vaccines, vaccine compositions, and methods of producing same. More particularly, this invention relates to vaccine compositions and methods for protecting animals against diseases associated with infection by toxigenic strains of Pasteurella multocida.
BACKGROUND OF THE INVENTION
Pasteurella multocida has been associated with disease in many species of animals, including man, bovine, ovine and porcine animals. It typically affects the nasopharyngeal regions and lungs of infected animals. For example, in a mixed infection with Bordetella bronchiseptica toxigenic strains of P. multocida, capsular type A or D, cause atrophic rhinitis in swine. Atrophic rhinitis (AR) results in atrophy of the nasal turbinates and deformities of the snouts and faces of pigs.
The pathogenicity of P. multocida is due in large part to the production of a potent necrotizing toxin, also called dermonecrotizing toxin (DNT), which will be referred to hereinafter as "the toxin". The toxin has been characterized as a heat-labile protein with a molecular weight of approximately 140,000 to 160,000.
P. multocida is distinguishable from other species of pasteurella on the basis of its growth characteristics, as follows: hemolysis: negative (90%); growth on MacConkey's agar: negative; indole production: positive; urease production: negative; and mannitol metabolism: positive. See, Zinsser, Microbiology, edit. by Joklik et al., Appleton-Century-Crofts, New York, 1980, pages 791-793, which is incorporated herein by reference.
Currently available vaccines for protecting animals from diseases associated with infection by P. multocida, include inactivated toxigenic P. multocida cells, inactivated preparations of partly purified P. multocida toxin and combinations of P. multocida cell-free preparations with other inactivated P. multocida strains or B. bronchiseptica strains. Foged et al, Vet. Record, 125: 7-11 (1989)!. These vaccine preparations, however, are not fully protective against disease because they fail to elicit effective amounts of the antibody that neutralizes the toxin, known as "antitoxin".
There remains a need in the art of veterinary practice for effective vaccines against infection of animals by toxigenic P. multocida.
SUMMARY OF THE INVENTION
The present invention provides novel vaccine compositions and components which protect animals against disease associated with infection by toxigenic Pasteurella multocida. These vaccine compositions are characterized by the ability to elicit significant quantities of circulating antitoxin.
In a first aspect, the invention provides a novel vaccine composition containing a whole Pasteurella multocida killed cell (bacterin) with cell-bound toxoid. This composition can induce in a previously unvaccinated animal a superior antitoxin response compared to the free, soluble toxoid. This composition is associated with a carrier suitable for internal administration, preferably aluminum hydroxide gel.
In another aspect, the invention provides a novel vaccine composition comprising (1) a whole Pasteurella multocida bacterin with cell-bound toxoid which, upon internal administration to an animal, induces an antitoxin response, and (2) a free, soluble toxoid of P. multocida. This vaccine composition produces an unexpected synergistic antitoxin response, much greater than the sum of the separate effects of the two components. A carrier is desirably associated with this composition.
The soluble cell-free toxoid of P. multocida is produced by a method that employs subjection of the toxin to varying pH and temperature, which method is also a novel aspect of the present invention. The term "toxoid" describes a preparation of the toxin that has been inactivated ("toxoided") by a process that abolishes its toxicity without destroying its ability to induce the production of the specific neutralizing antitoxin.
In a further aspect the above vaccine compositions may be varied by combination with an immunogenic amount of one or m
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Frantz Joseph C.
Kemmy Richard J.
Roberts David S.
Swearingin Leroy A.
Ginsburg Paul H.
Koller Alan L.
Pfizer Inc.
Richardson Peter C.
Sidberry Hazel F.
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