Polypeptide fragments capable of competition with Streptococcus

Details Polypeptide fragments capable of competition with Streptococcus Polypeptide fragments capable of competition with Streptococcus

1997-10-20

2000-02-15

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...

4241851, 4242441, 530324, 530325, 530326, 530327, 530328, 530329, 530350, A61K 3900, A61K 3902, A61K 3909, C07K 500

Patent

active

060249587

DESCRIPTION:

BRIEF SUMMARY
This invention relates to polypeptide fragments of the Streptococcus mutans I/II antigen that are useful in treating and preventing dental caries.
Streptococcus mutans is the main etiological agent of dental caries, a disease which affects mammals including humans.
The S. mutans I/II antigen (SA I/II) is a cell surface protein with an M.sub.r of about 185 kDa. It is believed to comprise several antigenic epitopes and to be at least partly responsible for S. mutans adhesion to teeth.
SA I/II is described in British Patent No. 2,060,647, as are number antibodies to it. A putative 3.5 to 4.5 kDa fragment of SA I/II, "antigen X", has also been described in European Patent No. 0 116 472.
However, it has now become clear that "antigen X" is not a fragment of SA I/II at all. Rather, it is a separate protein that merely co-purifies with SA I/II. It is believed to be encoded by a separate gene.
Two large fragments of SA I/II, an N-terminal fragment (residues 39 to 481) and a 40 kDa central fragment (residues 816 to 1213) are recognised by human serum antibodies. Within the central fragment, 80% of the sera tested recognise elements within a proline-rich region (residues 839-955) that comprises three tandem repeats. This suggests that this region includes one or more B-cell epitopes. The central fragment (residues 816-1213) is also believed to comprise one or more adhesion sites that mediate S. mutans' attachment to the tooth.
The aim of the above-mentioned work has been the development of vaccines for immunisation against dental caries. However, precise identification of the antigenic epitopes within SA I/II is a prerequisite for designing synthetic vaccines based on it. Similarly, precise identification of adhesion sites is essential for the design of drugs against dental caries that rely on inhibiting S. mutans' adhesion to the tooth.
No antigenic epitopes (T-cell or B-cell epitopes) or adhesion sites within SA I/II have been characterised, nor has the precise location of any such regions been suggested. Also, there has been no indication of the location of S. mutans' T-cell epitopes as the above-mentioned work has concentrated on S. mutans' ability to adhere to teeth and to generate a B-cell response.
The inventors have identified a number of T-cell epitopes, B-cell epitopes and adhesion sites within residues 803 to 1114 of SA I/II. Some of the T-cell and B-cell epitopes overlap or are contiguous with each other and/or with one or more of the adhesion sites.
The presence of a number of antigenic epitopes of both types and a number of adhesion sites within the same region of SA I/II could not have been predicted and the finding that some of the adhesion sites and epitopes overlap or are contiguous with each other is particularly surprising.
These findings make it possible to design effective synthetic vaccines against dental caries as well as drugs that engender resistance against the disease or alleviate pre-existing cases of it by preventing S. mutans' adhesion to the tooth. Further, the surprising finding that some of the T-antigenic epitopes and the adhesion site are contiguous or overlapping makes it possible to design bifunctional drugs that effect immunisation against dental caries as well as preventing adhesion of S. mutans to the tooth.
Accordingly, the present invention provides a nucleic acid sequence which codes upon expression in a prokaryoic or eukaryotic host cell for a polypeptide product having one or more properties selected from (i) the ability to adhere to a mammalian tooth in a competitive manner with naturally occurring Streptococcus mutans antigen I/II, thus preventing or diminishing the adhesion of S.mutans to the tooth; (ii) the ability to stimulate a T-cell response; and (iii) the ability to stimulate a B-cell response, said nucleic acid sequence being selected from: strands thereof; which hybridise to the sequences defined in (a) over at least 70% of their length; which, but for the degeneracy of the genetic code, would hybridise to the nucleic acid sequences defined in (a) or (b) over

REFERENCES:
patent: 5258368 (1993-11-01), Lewicki et al.
Moisset et al: Infection and Immunity, vol. 62 No. 1, Jan. 1994, pp. 183-193.
Munro et al.: Infection and Immunity, vol 61 No. 11, Nov. 1993, pp. 4590-4598.
Munro et al.: J. Dent. Res. 71 (IADR Abstracts); 1992, 7235, Abstact 1753.
Kelly et al.: J. Dent. Res. 71 (IADR Abstracts); 1992, 517, Abstract 17.
Kelly et al.: Infection and Immunity, vol. 63 No. 9, Sep. 1995, pp. 3649-3658.
Simitsek et al.: J. Exp. Med. 4181, Jun. 1995, pp. 1957-1963.
Watts and Lanzavecchia: J. Exp. Med. 4178, Oct. 1993, pp. 1459-1463.
Barnett et al.: Eur. J. Immunol. 19 (1989) pp. 515-521.
Adorini et al.: The Jounal of Experimental Medicine, vol. 168, Dec. 1988, pp. 2091-2104.
Smith-Gill et al.: The Journal of Immunology, vol. 125 No. 1, Jan. 1982, pp. 314-322.
Sheriff et al.: Proc. Natl. Acad. Sci., USA 84 (1987) pp. 8075-8079.
Charles et al.: Eur. J. Immunol., 1991, 21, pp. 1147-1153.
Emsly et al.: Nature 4381, May 1986, pp. 90-92.
Jacobs et al.: J. Med. Microbiol., vol. 43 (1995), pp. 422-429.
Neurath et al.: Cell, vol. 46, pp. 429-436, Aug. 1.sup.st, 1986.
Neutath et al.: Exp. Med 4175, Feb. 1992, pp. 461-469.
Greenstein et al.: The Journal of Immunology, vol. 148, pp. 3970-3977, (1992).
Steward et al.: Vaccine vol. 11, issue 14, 1993, pp. 1405-1414.
Brady et al.: Infection and Immunity, vol. 16, No. 3, Mar. 1992, pp. 1008-1017.
Lehner et al.: "T-Ce;; and B-Ce;; T-Cell and B-Cell Eptiope mapping and construction of peptide vaccines"; Cjhapter 24 in "Molecular Pathogen esis of Periodontal Disease", edited by Robert Geneco et al., .COPYRGT. 1994 American Sociey for Micobiology.
Abstracts 234 (Kendal et al.), 235 (Todryk et al.) and 238 (Ma et al.); J. Dent Res., Apr. 1994, vol 73, No. 4.
Kelly et al.: Immunology, vol. 87, pp. 55-63, (1995).
Lazar et al. Mol. Cell. Biology 8(3):1247-52, Mar. 1988.
Burgess et al. J.Cell Biology 111:2129-38, Nov. 1990.
Solgaller et al. Caner Immunol. Immunother. 105-116, 1994.

Affiliated with

Also associated with

Rating

Polypeptide fragments capable of competition with Streptococcus does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Polypeptide fragments capable of competition with Streptococcus , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polypeptide fragments capable of competition with Streptococcus will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1903566