Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1991-01-10
1993-03-30
Nucker, Christine M.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530300, C07K 1300
Patent
active
051985357
ABSTRACT:
A protein antigen (SSP2) on the surface of Plasmodium sporozoites is disclosed as a candidate immunogen for vaccination against malaria. This use of this protein, which is distinct from the extensively characterized circumsporozoite (CS) protein, will also facilitate research into host immunological responses to malaria. This antigen is detected by a monoclonal antibody (NYS4) which is specific for a 140 kilodalton (kD) protein on the sporozoite cell surface. Immunoreactive genomic clones are described which express this surface antigen gene and the primary nucleic acid sequence and the deduced amino acid sequence derived from this DNA sequence are disclosed. Unique repetitive sequences of amino acids are described which further demonstrate the distinction between SSP2 and the CS protein. A synthetic peptide containing repeating epitopes of SSP2 derived protein antigen and which are substantially shorter in length than the intact antigen are disclosed. The peptide when administered to a host elicits antibodies which bind to the SSP2 protein on the sporozoite surface. A recombinant plasmid bearing SSP2 DNA sequences expresses SSP2 epitopes in mammalian cells and the introduction of these transfected cells into mice elicits antibody and cytotoxic T-cell lymphocytic responses which confer partial protection to the recipient animals against challenge infection. In combination, the SSP2 protein and the CS protein elicit immunological responses in the mammalian host which confer 100% protection against challenge infection.
REFERENCES:
Khusmith et al, Science vol. 252:715-718 May 1991. "Protection against Maia by Vaccination with Sporozoite surface protein 2 plus CS protein", not prior art, for information.
Walliker et al. Science vol. 236 Jun. 1987, Genetic Analysis of the Human Malaria Parasite Plasmodium falciparum.
Charoenvit et al. Inf. & Imm vol. 55 1987 pp. 604-608, Characterization of Plasmodium yoelii.
Monoclonal anlitsedes directed against stage-specific sporozoite antigens.
Hollingdale et al., Imm Letters vol. 25.
Non-CS pre-erythrocytic protection antigens Immunology Letter 25 1990.
Robson et al.; A Highly Conserved Amino-Acid Sequence . . . ; Sep. 1, 1988; Nature, vol. 335, p. 79.
Charoenvit Yupin
Hedstrom Richard
Hoffman Stephen L.
Khusmith Srisin
Rogers, IV William O.
Garvert William C.
Nucker Christine M.
Sidberry Hazel
Spevack A. David
The United States of America as represented by the Secretary of
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