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
1987-04-09
1997-12-23
Vogel, Nancy T.
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
530326, 530300, 530350, C07K 708, C07K 14445
Patent
active
057009066
DESCRIPTION:
BRIEF SUMMARY
This application incorporates by reference the entire disclosure of the following copending commonly assigned U.S. Patents:
U.S. Pat. No. 4,466,917 corresponding to application Ser. No. 574,124, and U.S. Pat. No. 4,915,942 corresponding to application Ser. No. 649,903.
BACKGROUND OF INVENTION
The present invention relates to the field of antigens suitable for providing protective immunity against malaria when incorporated into a vaccine. Malaria constitutes a worldwide public health hazard of enormous economic and medical significance. The disease contributes substantially to infant mortality in endemic areas and remains a severe and debilitating illness for those who remain afflicted with it as adults. Despite advances in the techniques of mosquito abatement and improved public health measures, regions where the disease is considered endemic are increasing in area. Furthermore, the risk of infection was substantially increased in some parts of the world because of the occurrence of new drug-resistant strains of the malaria parasite.
This invention relates to the circumsporozoite (CS) protein of the sporozoite stage of Plasmodium vivax malaria parasite; to a DNA fragment coding for such protein; to immunogenic peptides and proteins comprising an amino acid sequence corresponding to the immunodominant epitope of said CS protein or immunologically active fragments thereof; and to DNA fragments coding for such peptides.
The aforementioned proteins and peptides are useful in inducing an immune response in humans and other animals and in conferring protective immunity in such hosts against infection by P. vivax sporozoites. The DNA fragments are useful in a method for preparing the protein and peptides of the present invention, using known recombinant DNA techniques.
DESCRIPTION OF THE PRIOR ART
The causative agent of malaria is a protozoan of the genus Plasmodium. Individual species within the genus appear to have a restricted host range for the animals they infect. For example, P. berghei and P. yoeli are infective to rodents, P. knowlesi and P. cynomolgi are primarily infective to monkeys, while P. falciparum, P. vivax, P. ovale and P. malariae are the species primarily infective to humans. Despite species differences in host range, the life cycles, mode of infection, biochemistry and genetics of the various Plasmodium species are markedly similar.
The life cycle of Plasmodium is complex, the organism undergoing several distinct morphological changes involving the participation of a mammalian host and a mosquito vector. The parasite, in the sporozoite form, is introduced to the mammalian host through the bite of the mosquito vector. The sporozoites rapidly disappear from the blood stream and are next found as intracellular parasites of liver parenchymal cells. A blood infection ensues, characterized by the well-known clinical symptoms of malaria after a complex series of morphological and biochemical transitions. The parasite is then found in the red blood cells, where it continues its development. Substantial amounts of the parasite may be obtained from the red blood cells of infected patients.
Vaccine development, to provide protective immunity against malaria infection has been thwarted by the fact that the parasite's life cycle in the mammalian host is primarily intracellular. Except for brief periods of time, the parasite is protected from contact with the immune system. Two stages in the parasite's life cycle during which it becomes briefly exposed to the immune system are; 1) the interval following initial infection before sporozoites have successfully invaded the cells of the liver; and 2) the interval during which merozoites leave infected red blood cells and enter uninfected red blood cells. The transient exposure of the merozoite forms in the extracellular milieu has provided the basis for prior art attempts to develop host immunity to blood forms of the parasite. European published Patent Application Number 62924, discloses antigenic proteins useful in the making of a vaccine to provide imm
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Arnot David E.
Enea Vincenzo
Nussenzweig Ruth S.
Nussenzweig Victor
New York University
Vogel Nancy T.
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