Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Patent
1987-01-12
1989-06-20
Schain, Howard E.
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
4352521, 435883, 4352536, 424 858, A61K 37085
Patent
active
048407941
DESCRIPTION:
BRIEF SUMMARY
This invention concerns the immunisation of ruminants, including cattle, sheep and goats, against staphylococcal mastitis.
Staphylococcal mastitis is a condition affecting approximately 25% of Australian dairy cattle, which is estimated to cost the industry about $50,000,000 each year in lost milk production, culling, antibiotics and costly husbandry procedures.
Traditionally the disease is treated, on the appearance of clinical signs, by the infusion of antibiotics which are active against the infective organism Staphylococcus aureus. Such an approach is far from ideal. Apart from being curative rather than preventative, there are economic considerations such as the need for identification and individual treatment of affected animals and the unsuitability of antibiotic-contaminated milk for human consumption or processing. An additional problem is the increasing development of antibiotic-resistant strains of S.aureus. Attention has, therefore, turned towards the possibility of immunising animals against the infection.
Numerous attempts have been made to systemically immunise ruminants against mastitis pathogens using conventionally prepared vaccines delivered either subcutaneously or intramuscularly. Killed bacterial cells (Derbyshire (1960b), isolated bacterial cell walls (Singleton et al 1967), toxoids (Minett 1939), killed cell-toxoid preparations (Bracewell and Pattison 1958) all have been tried with and without immunological adjuvants (Derbyshire 1961a). In some of these experiments a degree of protection has been achieved but overall the results have been disappointing. In view of the outstanding successes of other systemically delivered bacterial vaccines in ruminants (for example, Clostridial vaccines, Brucella abortus strain 19) the failure of mastitis vaccines generally has been attributed to the efficiency of the blood-milk barrier in preventing all but small quantities of circulating antibody from reaching the milk (Lascelles and McDowell 1974).
There have been reports in the literature which (despite experimental limitations in each case) . are extremely interesting because of the apparent success achieved when immunising sheep (Bridre 1907) and goats (Derbyshire 1961b) with live S.aureus vaccines (given subcutaneously). In both of these studies it was reported that the vaccinated animals were highly resistant to subsequent intramammary challenge with virulent S.aureus. More recently research has confirmed the protective capability of a live S.aureus vaccine in ewes (Watson and Lee 1978) and elucidated some of the mechanisms which are probably involved. Live S.aureus vaccines stimulate the synthesis of considerable quantities of IgG.sub.2 antibody which is cytophilic for neutrophils and there is direct evidence that this antibody enhances the specific phagocytic capacity of neutrophils for S.aureus under in vitro conditions (Watson 1975b, 1976). In contrast to live staphylococcal vaccines which stimulate predominantly IgG.sub.2 synthesis (Kennedy et al 1981, Kennedy and Watson 1982), killed staphylococcal vaccines given with oily adjuvants stimulate the production of predominantly IgG.sub.1 antibody (Yokomizo and Isayama 1978; Kennedy and Watson 1982). Thus at least one probable reason for the relatively poor results with killed S.aureus vaccines in prophylaxis of staphylococcal mastitis is that they do not stimulate synthesis of sufficient quantities of the subclass of IgG which mediates protection through its opsonising activity Furthermore, recent studies in non-lactating ewes have shown that a live S.aureus vaccine was superior to a killed vaccine in promoting an enhanced neutrophil response in the mammary gland to a subsequent intramammary challenge with viable staphylococci of a heterologous strain (Colditz and Watson 1982a, 1982b). The live vaccine, therefore, results in more neutrophils arriving in the secretion within a few hours of infection and these cells are "armed" with cytophilic IgG.sub.2 which increases their phagocytic capacity for staphylococci. In remains to be determined
REFERENCES:
patent: 4327082 (1982-04-01), Armitage
patent: 4425330 (1984-01-01), Norcross et al.
patent: 4591499 (1986-05-01), Linn et al.
Infection & Immunity, Jul. 84, pp. 87-93, vol. 45, No. 1, Fournier et al., "Purification . . . Staphylococcus aureus Type 8. . . ".
Carb. Research, 117 (1983), 113-123, Murphy et al., "Repeating Sequence of . . . Capsular Polysaccharide".
Chem. Ab., vol. 100, 1984, p. 292 (100:20338c) "Models to Study Antigenic and Virulence Prop . . . ".
Chem. Ab., vol. 96, 1982, p. 384 (96:177569a) "Capsular Polysaccharides of Staphylococcus aureus".
Chem. Abstracts, 91 (1979), 173120w, Watson et al.
Commonwealth Scientific and Industrial Research Organization
Schain Howard E.
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