Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1994-10-07
1998-09-29
Cunningham, Thomas M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 235, 4242681, 4242721, 530350, 530395, A61K 31505, C07K 14445
Patent
active
058146172
ABSTRACT:
An IgG1 monoclonal antibody, Navy Yoelii Liver Stage 3 (NYLS3) does not recognize sporozoites, but recognizes P. yoelii liver stage parasites within 6 hours of invasion of mouse hepatocytes, and throughout the hepatic and asexual erythrocytic stages of the life cycle. When added to primary cultures of mouse hepatocytes 24 hours after inoculation with P. yoelii sporozoites, when all sporozoites have invaded hepatocytes, NYLS3 eliminates up to 98% of liver stage parasites. Intravenous injection of NYLS3 into mice delays the onset and reduces the density of blood stage parasitemia after sporozoite or blood stage challenge. The protein recognized by this mAb is identified and designated P. yoelii hepatic and erythrocytic stage protein, 17-kDa or PyHEP17. The gene encoding PyHEP17 and a DNA vaccine comprising exons of the DNA that encodes PyHEP17 are disclosed. A DNA vaccine consisting of exon 1 and part of exon 2 of the gene encoding PyHEP17 protects 86% of A/J mice, 33%-43% of B10.BR mice, 17%-29% of BALB/c mice and 14%-20% of B10.Q mice from development of blood-stage parasitemia. A combination of DNA vaccines consisting of a PyHEP17 DNA vaccine and a PyCSP DNA vaccine confers complete protection against development of blood-stage parasitemia in BALB/c mice and 71% protection in A/J and B10.BR mice. This DNA vaccine-induced protection may be additive. Combinations of other malaria antigens are covered. The application discloses the P. falciparum homolog of PyHEP17 and includes the means of identification of the PyHEP17 homologs of the other Plasmodium species which infect humans, specifically P. vivax, P. ovale and P. malariae.
REFERENCES:
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Caspers et al., "A Plasmodium falciparum malaria vaccine candidate which contains epitopes from the circumsorozoite protein and a blood stage antigen, 5.1" Molecular and Biochemical Parasitology, 47, pp. 143-150 (1991). Plasmodium falciparum Vaccine Candidate in Adults" Trop. Geogr. Med 44 pp. 9-14 (1992).
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Doolan et al., "Circumventing Genetic Restrictions of Protection Against Malaria with Multi-Gene DNA Immunizatio: CD8+ T Cell, Interferon-.gamma., and Nitric Oxide Dependent Immunity" J. Exp Med (in press).
Doolan et al., "Characterization of the Protective Hepatocyte Erythrocyte Protein 17 kDa Gene of Plasmodium Yoelli: Homolog of Plasmodium Falciparum Exported Protein 1" (submitted for publication).
Charoenvit Yupin
Doolan Denise L.
Hedstrom Richard C.
Hoffman Stephen L.
Cunningham Thomas M.
Spevack A. David
The United States of America as represented by the Secretary of
LandOfFree
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