Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1986-02-19
1989-01-03
Warden, Robert J.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
424 92, 435820, 436543, 530325, 530326, 530327, 530328, 530329, 530330, 530350, 530403, 530806, 530825, 935 65, A61K 3902, C07K 1500, C07K 1504
Patent
active
047958030
DESCRIPTION:
BRIEF SUMMARY
The present invention relates, inter alia, to an antigen useful, e.g., for the immunization of a mammal, an antibody raised against it, and a vaccine produced from it.
Antigens composed of several proteins which together form a distinct phenotype in a pathogenic bacterial strain or species, and which must therefore be assumed to contain a large number of immunogenic determinants, are well known. However, such antigens--and vaccines produced from them--have a number of disadvantages: in particular, they have a tendency to be too selective in that, on immunization, antibodies are formed against each of these immunogenic determinants which together identify the one particular bacterial strain from which the antigen has been derived, but not other bacterial strains of the same species so that immunization is only effected against this particular strain, but not other, closely related strains of the same species.
The present invention is an attempt to overcome these disadvantages by providing an antigen which substantially only comprises the immunogenic determinant(s) which lead to the desired immunity and which is furthermore not limited to one particular strain of the pathogenic bacteria in question.
It has become increasingly clear that the capacity of many pathogenic bacteria to adhere to the surface of cells is of primary importance for the initiation of many infectious diseases (Beachey, J. Infect. Dis. 143, 1981, pp. 325-345). This adhesion capacity is caused by the presence of receptors on mammalian tissue cells, such as epithelial cells, or on mammalian erythrocytes, which receptors, due to their configuration, form bonds with adhesin polypeptides. (In the present context, the term "adhesin polypeptide" is intended to indicate both a polypeptide specifically required for the adhesion phenotype and, more generally, a polypeptide in whose absence adhesion does not take place (for whatever reason). Each receptor is assumed to bond with a different adhesin structure. The receptor may be a peptide receptor, such as an amino acid present on a sugar, or--more usually--a carbohydrate such as neuramic acid-(2.fwdarw.3)-galactose, mannose-.alpha.-(1.fwdarw.2)-mannose or digalactoside (the .alpha.-D-Galp-(1.fwdarw.4)-.beta.-D-Galp moiety present in the globoseries of glycolipids which in the present context is occasionally termed the globoside).
In many pathogenic bacteria, the adhesin polypeptide proper is believed to form only part of a larger sequence of polypeptides which are all, in one way or another, related to the adhesion function (e.g. polypeptides which mediate the transport of the adhesin through the cell wall or anchor it to the outer surface of the cell wall and so on), and in accordance with the aim of the present invention, a specific adhesin polypeptide is identified among the other polypeptides of the sequence and used as an antigen. This is thought to constitute a less selective identification marker so that antibodies will not only be raised against the strain from which the antigen is derived but also against the other pathogenic strains of the same bacterial species.
Accordingly, the present invention relates to an antigen which, as its major immunizing component, comprises a determinant of an adhesin polypeptide or an immunogenically active subsequence thereof or a precursor therefor which is convertible to an immunologically active form, antibodies against which determinant react with the adhesin polypeptide produced by pathogenic adhesin-forming bacteria which adhere to mammalian tissue. This antigen may comprise an amino acid sequence of at least 5 amino acids and up to the entire amino acid sequence of the adhesin polypeptide.
The adhesin polypeptide may conveniently be derived from adhesin-forming bacteria. This group of bacteria comprises both grampositive and gramnegative bacteria, and the bacterial species of the greatest interest in the present context from which it would be advantageous to derive one or more specific adhesin polypeptides are uropathogenic or enteropathogenic strai
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patent: 4443431 (1984-05-01), Buchanan et al.
patent: 4454117 (1984-06-01), Brinton
patent: 4521334 (1985-06-01), Beachey
patent: 4652448 (1987-03-01), Sadowski
patent: 4657849 (1987-04-01), Kallenius et al.
G. Dougan et al., Journ. Bact. 153, 364-370 (1983).
F. R. Mooi et al., Journ. Bact. 150, 512-521 (1982).
Baga Britt M.
Goransson Mikael
Lark David L.
Lindberg Frederick C.
Lund Bjorn O.
Saunders David A.
Syn-Tek AB
Warden Robert J.
White John P.
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