Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1994-07-15
1998-11-24
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
4242341, 4242431, 530350, 435 681, 435 692, 435216, A61K 3909
Patent
active
058403159
DESCRIPTION:
BRIEF SUMMARY
This application is the U.S. national stage of PCT/GB93/00110, filed Jan. 18, 1993, which International Application claims priority Great Britain application No. 9201013.1 filed Jan. 17, 1992.
This invention relates to vaccination against diseases caused by pathogens, and more particularly to vaccination against mastitis.
To cause clinical mastitis in the bovine udder a bacterium must either grow within the gland at a rate sufficient to avoid removal in the secretion or must colonise normal secretory and/or ductular tissues. More virulent strains of bacteria may resist phagocytic killing despite the presence of large numbers of polymorphonuclear leucocytes. Certain species of bacteria are known to produce haemolytic and/or cytolytic toxins which may have a role in the pathogenesis of the disease.
To date, vaccines to protect the mammary gland from clinical mastitis have attempted to promote more efficient phagocytosis and killing of bacteria (by the production of opsonising antibody) or to inactivate toxic products (by the production of neutralising antibody).
Streptococcus uberis is a common cause of bovine mastitis responsible for around 20% of all clinical cases in the UK (Bramley and Dodd 1984). The ability of this organism to infect the lactating mammary gland is dependant on its ability to grow in the secretion and avoid phagocytosis by bovine neutrophils (Leigh et al 1990).
The majority of nitrogen in bovine milk is present in the form of protein (Aston 1975) and, in the absence of proteolysis, bacterial growth in milk is limited by the lack of free amino acids. This is highlighted by the dependence of the lactic streptococci on extracellular, caseinolytic proteinases for growth in milk (Mills and Thomas 1981). The ability of bacteria to grow in mastitic milk is enhanced by the presence of the caseinolytic enzyme plasmin (Marshall and Bramley 1984). The transformation of plasminogen to plasmin requires plasminogen activators which are known to occur in blood plasma and animal tissues (Collen 1980). Certain streptococci are capable of producing streptokinase which activates plasminogen to plasmin but no previously isolated streptokinase activates bovine plasminogen.
According to one aspect of the present invention, there is provided a vaccine for use to treat or prevent a disease in a vertebrate, the vaccine comprising an antigenic entity and a carrier, the antigenic entity being adapted to cause, following vaccination of the vertebrate with the vaccine, an immune response generating antibodies which inhibit a factor from a pathogen which, directly or indirectly, causes breakdown of protein in the vertebrate wherein said breakdown enhances growth of the pathogen.
Antibodies which "inhibit" the factor are those which diminish to a useful extent the ability of the factor to cause the said breakdown of the vertebrate protein. Preferably, for any given interaction between an individual antibody and a molecule of the factor, the said ability is reduced to zero. Suitably, the antibodies are secreted into the environment where the factor acts. Thus, in the case of vaccines against mastitis, the antibodies should be secreted into the milk.
Streptococci are responsible for certain types of dental caries, thus, in the case of dental caries, the antibodies should be secreted into the saliva or present in the mucous membranes associated with the gums and lining of the mouth.
Suitable carriers and adjuvants etc for formulating the antigen entity into a vaccine are known.
Pharmaceutically acceptable carriers may, for example, be liquid media suitable for use as vehicles to introduce the antigenic entity into the vertebrate. An example of such a carrier is saline solution. The antigenic entity may be in solution or suspended as a solid in the carrier.
The vaccine formulation may also comprise an adjuvant for stimulating the immune response and thereby enhancing the effect of the vaccine. Convenient adjuvants for use in the present invention include, for example, aluminium hydroxide and aluminium phosphate.
The vacc
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Ginsburg Paul H.
Housel James C.
Koller Alan L.
Pfizer Inc.
Richardson Peter C.
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