Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1994-11-28
1998-10-06
Caputa, Anthony C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4241921, 42419711, 4242391, 435 693, 436544, 436545, 436546, 530324, 530402, 530412, 530825, A61K 3908, C07K 1433
Patent
active
058173170
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel peptides capable of illiciting an immunological response that is protective against Clostridium perfringens in man or animals; more particularly to novel peptides capable of illiciting such protective response against the alpha-toxin of that organism, and antibodies and antisera raised thereto. Preferred agents enable prophylaxis and treatment of Clostridium perfringens induced disease states in both humans and other animals.
Clostridium perfringens (C. perfringens) is ubiquitous in the environment and has been found in the soil, decaying organic matter and as part of the gut flora in man and animals. Different strains of C. perfringens can be assigned to one of five biotypes (A-E) depending on the spectrum of toxins produced (McDonel (1986) Pharmacology of Bacterial Toxins; F Dorner and J Drews (Editors) Pergamon Press, Oxford). Biotype A strains are of particular importance as the etiological agents of gas gangrene in man. The disease is of increasing significance in the elderly and in diabetic populations, especially in those who have undergone lower limb surgery, where impaired blood supply to tissues can lead to anoxic conditions suitable for multiplication of the bacterium. The disease can also arise in patients who have undergone surgery of the gastrointestinal tract when contamination of damaged tissues with gut contents can result in its establishment. A more periodic increase in the incidence of gas gangrene has been shown to occur during armed conflicts when deep tissue wounds are contaminated with soil and the failure to promptly treat such injuries resulted in the death of several hundred thousand combatants during World War I.
The pathogenesis of gas gangrene can be largely attributed to the production of potent exotoxins by the bacterium, of which the alpha-toxin has received attention as the major contributor to the disease. The toxin may act peripherally to the initial focus of infection by damaging and reducing the blood supply to tissues thus promoting the conditions required for spread of the infection.
In the later stages of the disease the toxin may act sytemically causing death. A crude C. perfringens toxoid vaccine was demonstrated to provide protection against experimentally induced gas gangrene as long ago as 1937 (Penfold and Tolhurst (1937) Medical Journal of Australia, pp 604)) and subsequent studies suggested that the effective component of this vaccine was derived from the alpha-toxin ( Robertson and Keppie (1943), Lancet 2 p311; Boyd et al (1972) J. Med. Microbiol 5, p467; Kameyama (1975) Japanese Journal of Medicine, Science and Biology 25, p200). In spite of these advances a vaccine has not been developed for use in humans and current treatment for gas gangrene usually involves the removal of the affected limb or tissues.
C. perfringens has also been identified, or implicated, as the causative agent of other diseases, for example in colic and enterotoxaemia, in horses, rabbit, cattle, sheep and poultry. Vaccines for use in such animals have been described in a number of prior patent applications, eg U.S. Pat. No. 4,2654,588, U.S. Pat. No. 4,292,307, GB 2030451, SU 152943, GB 968199, GB 958575, GB 958574 and GB 958564; all being formal toxoids or equivalents.
The present inventors have previously isolated the gene encoding the alpha-toxin ( Titball et al (1989) Infection and Immunity, Vol 57, p357-376) and examined structure-function relationships of the protein (Titball and Rubidge 1990; Titball et al (1991) Infection and Immunity, Vol 59, p1872-1874). As part of these studies the location of some antibody epitopes were determined (Logan et al (1992) Infection and Immunity, Vol 59, p4338-4382).
It is an object of the present invention to provide novel vaccines capable of inducing production of protective antibodies directed against C. perfringens alpha-toxin (CPa) when administered to animals or man and thereby providing prophylaxis against infection by C. perfringens, disease states resulting from such infection, and/or the alpha-tox
REFERENCES:
patent: 4877612 (1989-10-01), Berger et al.
patent: 5200318 (1993-04-01), Rabin et al.
Logan et al. Infection and Immunity 59(12):4338-4342, Dec. 1991.
Titball et al. Infection and Imunity 57(2): 367-376, Feb. 1989.
Titball et al., Hemolytic and Sphingomyelinase Activities of Clostridium fringens Alpha-Toxin Are Dependent on a Domain Homologous to That of an Enzyme from the Human Arachidonic Acid Pathway, Infection and Immunity 59, 1872-1874 (1991). See entire article.
Basic & Clinical Immunology, H. Fudenberg et al. eds., Lange Medical Publications 1980. see ch. 44 pp. 722-736.
Titball Richard William
Williamson Ethel Diane
Caputa Anthony C.
The Secretary of State for Defense of Great Britian & Northern I
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