Renibacterium salmoninarum vaccine

Details Renibacterium salmoninarum vaccine Renibacterium salmoninarum vaccine

2000-04-05

2003-09-30

Graser, Jennifer E. (Department: 1645)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Bacterium or component thereof or substance produced by said...

C424S184100, C435S243000, C435S252100

Reexamination Certificate

active

06627203

ABSTRACT:

Protection of farmed fish against bacterial disease caused by
Renibacterium salmoniarun
by the use of a live strain of Arthrobacter spp. The working designation of this species, RSxII, is used through this document.
This invention relates to the protection of farmed fish against disease caused by the bacterial species
Renibacterium salmoninarum
. This disease colloquially named bacterial kidney disease or BKD from some aspects of it pathology, is one of the most economically serious diseases in salmonoid culture. Conservative estimates suggest that losses on the west coast of Canada exceed 20 million dollars annually. Similar problems have occurred in Chile and the Pacific coast of the USA. The farming of some species, such as Chinook and Coho salmon, has become economically unsustainable in these areas due to this disease. In cooler waters such as Easter Canada and Northern Europe, the disease is characterised by less severe symptoms and gives rise generally to chronic infections. The consequent poor growth performance and increased susceptibility to concurrent disease cause a high economic loss in these industries also.
A number of the standard methods for the production of effective vaccines have been used in efforts to provide protection against
Renibacterium salmoninarum.
Generally these have proved to be ineffective and, where successes have been reported by particular groups, these have provided unreplicable in the hands of others. Such methods have employed killed cells and cell fragments with or without adjuvants.
The key factor in this lack of success is probably the ability of Renibacterium to survive and possibly multiply within the macrophages of the host fish. In this situation it is protected from the main immune systems of the host. Constant “leakage” of cells from the macrophages causes a low-level persistent infection which constantly challenges the fish immune system. Controlling this under normal conditions lowers the fitness of the animal and, if a further environmental or disease stress occurs, the Renibacterial cells may initiate a more damaging infection. Sometime during this process a full immune response may be mounted to the disease but this proves to be ineffective since large quantities of a 57000 kilodalton protein are produced by Renibacterium which induces the production of large quantities of antibodies which are not protective. The “preoccupation” of the humoral immune system with this protein prevents an effective response being made to other components of the bacteria which might confer protection. The p57 protein therefore acts as an effective decoy.
The most successful of the approaches to vaccination against Renibacterium have all used Freund's Complete Adjuvant (FCA). This aids in the effective presentation of antigens to the T-cells in the normal way but is also, independently, a powerful stimulator of the non-specific cellular immune responses. FCA contains cell wall fragments obtained from species of Corynebacterium. The taxonomic relationships between bacteria recognised under this and associated genera are not clear and Renibacteria were originally classified as Corynebacteria. Some strains of Renibacteria also have powerful stimulators of non-specific immunity on their cell surfaces further suggesting a close taxonomic relationship. The closely relates genus Arthrobacter also contains species which have similarly reactive groups on their surface capable of stimulating non-specific immunity. Cells of this genus, not capable of causing disease but containing such groups on their surface and probably also antigens in common with Renibacterium, might reasonably be expected to stimulate powerful specific and non-specific immunity conferring protection against disease. The use of such Arthrobacter as live cells, capable of surviving inside macrophages, would prolong the stimulation and extend protection for a commercially acceptable period of time.


REFERENCES:
patent: 5192676 (1993-03-01), Morgan
patent: 96/11717 (1996-04-01), None
Mori et al. Bull. JPN Soc Sci Fish, 46(6): 717-722, 1980, Abstract only.*
Karaskiewicz, J. Pr. Inst. Naft. Poland, V20505/IB, 1974, p. 67, Abstract only.*
Koch et al., “16S rDNA studies on membranes of Arthrobacter and Micrococcus: An aid for their future taxonomic restructuring”, FEMS Microbiology Letters 123, 1994, pp 167-171.
S.G. Griffiths et al., “Reduction of Renibacterium Culture Activity in Atlantic Salmon Following Vaccination with Avirulent Strains”, Fish & Shelfish Immunology, vol. 8, pp. 607-619, (1998).

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