Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1996-12-02
2000-09-26
Navarro, Mark
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530412, 530414, 530415, 530417, 530419, 530421, 514 2, C07K 100, C07K 1400, C07K 1600, A23J 100
Patent
active
061244325
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a medicament for prophylaxis of swine infectious diseases. More particularly, the present invention relates to an improved toxoid of dermonecrotic toxin produced by Bordetella, a toxoid mixture comprising said toxoid and a toxoid of dermonecrotic toxin produced by Pasteurella and a process for preparing said toxoid.
BACKGROUND OF THE INVENTION
Atrophic rhinitis (hereinafter also referred to as "AR") is a swine chronic respiratory disease which has extremely potent infectivity with primary symptoms being turbinate atrophy, hypoplasia, epistaxis, twisting of the snout and induction of other respiratory diseases, and the like. This disease is known to be caused by a toxigenic Bordetella bronchiseptica (hereinafter also referred to as "Bb") and a toxigenic Pasteurella multocida (hereinafter also referred to as "Pm") which infect at the mucosa of an upper respiratory tract. Bb possesses hemagglutinin and pili as an adherence factor and thus easily attaches to the nasal mucosa while Pm does not have such an adherence factor and hence hardly colonizes by itself. Accordingly, for the establishment of Pm infection, a predisposing factor causing a lesion at the nasal mucosa is necessary, said factor being typically Bb. Pathological factors involved in the cause of lesion in the nasal mucosa are known to be a tracheal cytotoxin and a dermonecrotic toxin. In an experimental infection, a pig is infected with Bb, and several days later, followed by intranasal infection with Pm, to cause a severe AR as observed in a field farm.
Bordetella includes B. pertussis, B. parapertussis, B. bronchiseptica, B. avium, and the like, which produce a variety of biologically active substances. Bb dermonecrotic toxin (hereinafter also referred to as "BbT") is one of such substances and is produced by any Bordetella. BbT having biological activities such as a hemorrhagic necrotic activity, an activity to cause turbinate atrophy, an activity to cause hypoplasia, a lethal activity, a vasoconstrictive activity in the smooth muscle, an activity to cause interruption in a local blood circulation, an activity to cause splenoatrophy, an activity to inhibit an antibody production, and the like was found to play an important role in Bordetellosis. Furthermore, it was found that BbT also plays an important role in the formation of pneumonic focus in piglets (Roop II, R. M. et al., Infect. Immun., 55, p.217-222 (1987)).
On the other hand, a part of Pasteurella multocida or a part of atypical Pasteurella produce Pm dermonecrotic toxin (hereinafter also referred to as "PmT"). PmT having biological activities such as a hemorrhagic necrotic activity, an activity to cause turbinate atrophy, an activity to cause hypoplasia, a lethal activity, an activity to cause interruption in a local blood circulation, an activity to cause splenoatrophy, and the like has been found to play an important role in the onset of disease by the toxigenic Pm. Furthermore, it was found that PmT is closely related to the formation of pneumonic focus in pigs by the toxigenic Pm (Iwatsu, S. and Sawada, T.; Jpn. J. Vet. Sci., 50, p.1200-1206 (1988)). Although both BbT and PmT are not secreted into a culture medium but accumulate within bacterial cells, they are released out of the bacterial cells into a culture supernatant due to bacteriolysis after a long term culture. In the in vivo process, dermonecrotic toxin released out of the bacterial cells due to bacteriolysis affect the living body.
Under the above-mentioned circumstances, the role of dermonecrotic toxin in protection in the living body still remains unclear, and for elucidating the mechanism of the protection, there is a need to develop a process for a large scale preparation of dermonecrotic toxin and to develop a toxoid of dermonecrotic toxin for use in prophylaxis of the disease. However, it has been difficult to purify dermonecrotic toxin due to its properties, i.e. unstability to heat, self-agglutination easily caused as purification processes pr
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Fujikawa Hideo
Kawai Toru
Takase Kozo
Ushijima Toshihiro
Juridical Foundation The Chemo-Sero-Therapeutic Research Institu
Navarro Mark
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