Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1993-04-08
1997-03-11
Cunningham, Thomas M.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4241941, 4242681, 4242721, 530300, 530350, 530395, A61K 39015
Patent
active
056098723
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new peptides, their use as active ingredients in vaccines and compositions containing same.
This application claims priority from PCT Application SE91/00541 and Swedish application 9002684.
BACKGROUND OF THE INVENTION
Malaria is a wide spread disease, particularly in the developing countries, and scientists are constantly looking for new means to control the dangerous parasitic disease caused by plasmodial parasites. Among these parasites Plasmodium falciparum causes the most severe disease, responsible for the major part of the mortality due to malaria.
One strategy in combatting malaria resides in the use of a conventional vaccine based on attenuated or dead malaria parasites, but such approach has not been found to be practically feasible.
The alternatives are constituted by development of modern techniques, such as the manufacture of proteins by chemical synthesis or by DNA technology, such proteins as components in subunit vaccines being able to induce protective immunity against the parasite infection.
One strategy in the selection of antigenic sequences to be included in a potential subunit vaccine against Plasmodium falciparum malaria is to define the epitopes of antibodies which have the capacity to interfere with the parasite life cycle. Properly presented in immunogens these epitopes are expected to induce protective antibody responses. With regard to the asexual blood-stages of P. falciparum, the main attention in this context has been made to antibodies with capacity to inhibit merozoite reinvasion in vitro (Anders, R. F. (1985) Candidate antigens for an asexual blood-stage vaccine. Parasitol. Today 1, 152-155). However, antibodies which inhibit the cytoadherence of infected erythrocytes to endothelial cells (Howard, R. J. (1988) Malarial proteins at the membrane of Plasmodium falciparum-infected erythrocytes and their involvement in cytoadherence to endothelial cells. Prog.Allergy 41, 98-147; Udomsangpetch, R., Aikawa, M., Berzins, K., Wahlgren, M. and Perlmann, P. (1989) Cytoadherence of knobless Plasmodium falciparum-infected erythrocytes and its inhibition by a human monoclonal antibody. Nature 338, 763-765) or inhibit rosette formation between uninfected and infected erythrocytes (Carlsson, J., Holmquist, G., Taylor, D. W., Perlmann, P. and Wahlgren, M. (1990) Antibodies to a histidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes. Proc.Natl.Acad. Sci. USA 87, 2511-2515) may also be of interest. Such antibodies are expected to interfere in vivo with the sequestration of late-stage infected erythrocytes (Howard, R. J. (1988) Malarial proteins at the membrane of Plasmodium falciparum-infected erythrocytes and their involvement in cytoadherence to endothelial cells. Prog.Allergy 41, 98-147; Carlson, J., Holmquist, G., Taylor, D. W., Perlmann, P. and Wahlgren, M. (1990) Antibodies to a bistidine-rich protein (PfHRP1) disrupt spontaneously formed Plasmodium falciparum erythrocyte rosettes. Proc.Natl.Acad.Sci. USA 87, 2511-2515).
The human monoclonal antibody (mAb) 33G2, obtained from an Epstein-Barr virus transformed B-cell originating from a Liberian P.falciparum-immune donor (Udomsangpetch, R., Lundgren, K., Berzins, K., Wahlin, B., Perlmann, H., Troye-Blomberg, M., Carlsson, J., Wahlgren, M., Perlmann, P. and Bj orkman, A. (1986) Human monoclonal antibodies to Pf155, a major antigen of malaria parasite Plasmodium falciparum. Science 231, 57-59) has several interesting biological properties. It inhibits both P.falciparum merozoite reinvasion in in vitro cultures (Udomsangpetch, R., Lundgren, K., Berzins, K., W ahlin, B., Perlmann, H., Troye-Blomberg, M, Carlson, J., Wahlgren, M., Perlmann, P. and Bj orkman, A. (1986) Human monoclonal antibodies to Pf155, a major antigen of malaria parasite Plasmodium falciparum. Science 231, 57-59) as well as cytoadherence of infected erythrocytes to melanoma cells in vitro (Udomsangpetch, R., Aikawa, M., Berzins, K., Wahlgren, M. and Perlmann, P. (1989) Cytoadherence of knob
REFERENCES:
Ahlborg, N., et al., Mol. Biochem. Parasitol. 46:89-96 (1991), "Definition of the epitope recognized by the Plasmodium falciparum-reactive human monoclonal antibody 33G2".
Berzins, K., Int. J. Immunopharmacol. (in press, 1994), "Development of vaccines against malaria".
Robbins Pathological Basis of Disease, 4th edition, R. S. Cotran, et al. (eds.), W. B. Saunders and Company, Philadelphia (1989). Pp. 402-406 only.
Cox, F. E. G., TIBTECH 9:389-394 (Nov., 1991), "Malaria vaccines--progress and problems".
Dubois, P., et al., Ann. Inst. Pasteur/Immunol. 139:557-567 (1988), "Structure and function of a thymic peptide is mimicked by Plasmodium falciparum peptides".
Groux, H., et al., Eur. J. Immunol. 20:2317-2323 (1990), "Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus".
Marglin, A., et al., Ann. Rev. Biochem 39:841-866 (1970), "Chemical synthesis peptides and proteins".
Mitchell, G. H., Parasitol, 98:S29-S47 (1989), "An update on candidate malaria vaccines".
Phillips, R. E., et al., Parasitology Today 2(10):2:271-282 (1986), "The pathophysiology of severe falciparum malaria".
Udomsangpetch, R., et al., J. Immunol. 142:3620-3626 (May 15, 1989), "Reactivity of the human monoclonal antibody 33G2 with repeated sequences of three distinct Plasmodium falciparum antigens".
Weir, D. M., Handbook of Experimental Immunology, second edition (1973), pp. A2.8-A2.12.
"Structure and Function of a Thymic Peptide is Mimicked by Plasmodium Falciparum Peptides", Ann. Inst. Pasteur/Immunol., P. Dubois et al., vol. 139, 1988. pp. 557-567.
Ahlborg Niklas
Berzins Klavs
Perlmann Peter
Cunningham Thomas M.
Malvac Foundation
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