Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor
Patent
1987-08-25
1992-05-26
Schwartz, Richard A.
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
Bacteria or actinomycetales; media therefor
435 698, 435 91, 4351723, 4352401, 43525233, 4353201, 536 27, 530350, 935 18, 935 27, 935 31, 935 41, 935 48, 935 56, 935 58, 935 65, 935 18, 935 73, 935 81, C12P 2106, C12P 1934, C12N 1500, C12N 500, C12N 1530, C12N 1570, C12N 121, C07H 1512, C07K 300
Patent
active
051167557
DESCRIPTION:
BRIEF SUMMARY
This invention relates to synthetic peptides and polypeptides which have antigenicity suitable for providing protective immunity against Plasmodium falciparum infections, and to methods for the production thereof.
The human malaria parasite Plasmodium falciparum encodes many polypeptides that elicit an immune response in man. Recently, molecular cloning techniques have facilitated the analysis of individual polypeptide antigens that are present in this complex mixture (1). Many cDNA clones encoding these antigens have been isolated by screening Escherichia coli colonies that express the cloned sequences with human antibodies. The production and screening of these clones is described in detail in International Patent Specification No. PCT/AU84/00016.
The present invention is based upon the identification and characterisation of further asexual blood-stage antigens of P. falciparum.
According to the present invention, there is provided a DNA molecule comprising a nucleotide sequence substantially corresponding to all or a portion of a base sequence coding for one of the antigens of P. falciparum described in detail hereinafter. In particular, there is provided a DNA molecule comprising a nucleotide sequence characterized by at least a portion thereof comprising all or a portion of a base sequence shown in the accompanying Figures. Such a nucleotide sequence codes for a polypeptide comprising at least a portion which corresponds to a portion of the amino acid sequence of an antigen of P. falciparum as described herein.
The present invention also extends to synthetic peptides or polypeptides displaying the antigenicity of all or a portion of an antigen of P. falciparum as described herein, as well as to compositions for stimulating immune responses against such an antigen in a mammal, which compositions comprise at least one synthetic polypeptide displaying the antigenicity of all or a portion of the antigen, together with a pharmaceutically acceptable carrier therefor. The synthetic peptides or polypeptides according to this aspect of the invention may be prepared by expression in a host cell containing a recombinant DNA molecule which comprises a nucleotide sequence as broadly described above operatively linked to an expression control sequence, or a recombinant DNA cloning vehicle or vector containing such a recombinant DNA molecule. The synthetic peptide or polypeptide so expressed may be a fusion polypeptide comprising in addition to a portion displaying the antigenicity of all or a portion of the antigen, an additional polypeptide coded for by the DNA of the recombinant DNA molecule. Alternatively, the synthetic peptides or polypeptides may be produced by chemical means, such as by the well-known Merrifield solid-phase synthesis procedure.
(I) A RHOPTRY PROTEIN OF P. falciparum
Intraerythrocytic asexual parasites of Plasmodium falciparum are responsible for the morbidity and mortality of this serious protozoal infection of man. Propagation of the asexual parasite occurs when mature schizonts rupture and release merozoites which invade fresh erythrocytes. Invasion begins when the merozoite abuts an erythrocyte and re-orientates so that the apex of the merozoite is in contact with the erythrocyte membrane. Paired apical organelles called rhoptries discharge their contents prior to perturbation of the erythrocyte membrane and subsequent entry of the merozoite. Rhoptry proteins have been implicated as potential protective immunogens in several systems (2, 3). A cDNA clone encoding a portion of a Mr 105,000 rhoptry protein of P. falciparum has now been identified and characterised. A rhoptry protein of this molecular weight is present in several isolates of P. falciparum from widely separated geographical areas.
Several previously isolated cDNA clones expressing P. falciparum antigens contained regions of tandemly repeated peptides. It has previously been shown that these repeat regions are frequently highly antigenic and are the immunodominant regions of the molecule recognized during natural infection. T
REFERENCES:
Odink et al. FEBS Lett vol. 173 pp. 108-112 (1984).
Kemp et al. Proc. Nat'l Acad Sci USA vol. 80 pp. 3787-3791 (1983).
Anders Robin F.
Brown Graham V.
Coppel Ross L.
Kemp David J.
Ellis Jean
Schwartz Richard A.
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