Plasmodium falciparum antigens inducing protective antibodies

Abstract

The invention provides novel preparations for a broad-spectrum antiplasmodial vaccine.

What is claimed is:  
     
         1 . A purified polypeptide selected in the group comprising the following peptides: 
 MSP3a: 167-YEKAKNAYQKANQAVLKAKEASSYD-191 (SEQ ID No: 11),    MSP3b: 184-AKEASSYDYILGWEFGGGVPEHKKEEN-210 (SEQ ID No: 12),    MSP3c: 203-PEHKKEENMLSHLYVSSKDKENISKEND-230 (SEQ ID No: 13),    MSP3d: 211-MLSHLYVSSKDKENISKENDDVLDEKEEEAEETEEEELEEK-251 (SEQ ID No: 14), and    combinations thereof.    
     
     
         2 . A long synthetic or recombinant polypeptide comprising epitopes contained within a MSP-3a peptide (SEQ ID No: 11), a MSP-3b peptide (SEQ ID No: 12), a MSP-3c peptide (SEQ ID No: 13), or a MSP-3d peptide (SEQ ID No: 14) and combinations of said peptides.  
     
     
         3 . An immunogenic composition comprising as an immunogen a long synthetic or recombinant peptide comprising epitopes contained within a MSP-3b peptide (SEQ ID No: 12), a MSP-3c peptide (SEQ ID No: 13), or a MSP-3d peptide (SEQ ID No: 14) and combinations of said peptides.  
     
     
         4 . A vaccine against malaria comprising a long synthetic or recombinant peptide comprising epitopes contained within a MSP-3b peptide (SEQ ID No: 12), a MSP-3c peptide (SEQ ID No: 13), or a MSP-3d peptide (SEQ ID No: 14) or combinations of said peptides, and a pharmaceutically acceptable carrier.  
     
     
         5 . The immunogenic composition of  claim 3  or the vaccine of  claim 4 , wherein said long synthetic or recombinant peptide further comprises the epitopes contained within a MSP-3a peptide (SEQ ID No: 11).  
     
     
         6 . The immunogenic composition of  claim 3  or the vaccine of  claim 4 , which is formulated for subcutaneous injection.  
     
     
         7 . The immunogenic composition or the vaccine of  claim 6 , comprising between 3 μg and 100 μg of a long synthetic peptide per injection dose.  
     
     
         8 . The immunogenic composition of  claim 3 , further comprising Alum and/or Montamide as an adjuvant.  
     
     
         9 . The vaccine of  claim 4 , wherein said pharmaceutically acceptable carrier comprises Alum and/or Montamide.  
     
     
         10 . A monoclonal antibody directed against a polypeptide according to  claim 1  or  claim 2 .  
     
     
         11 . A composition of purified polyclonal antibodies directed against a polypeptide according to  claim 1  or  claim 2 .  
     
     
         12 . A pharmaceutical composition comprising antibodies according to  claim 10  or  claim 11 .  
     
     
         13 . A method for immunizing against malaria an individual or a mammal that can contract malaria, comprising the step of administering to this individual or mammal in need of such immunization the immunogenic composition of  claim 3  or the vaccine of  claim 4 .  
     
     
         14 . The method of  claim 13 , wherein said immunogenic composition or vaccine is administered via subcutaneous injection.  
     
     
         15 . The method of  claim 8 , wherein said administration comprises two or three injections of said immunogenic composition or vaccine.  
     
     
         16 . A method for in vitro evaluation of a premonition state against malaria in an individual or a mammal that can contract malaria who has been immunized according to the method of  claim 7 , comprising the step of putting in contact a sample taken from said individual with a native MSP-3 protein from  Plasmodium falciparum , under conditions suitable for binding between said MSP-3 protein and antibodies present in the sample; and detecting the binding of said native MSP-3 with antibodies present in the sample, which is indicative of a premunition state.  
     
     
         17 . A method for in vitro prognosis of the fate of a cerebral malaria patient, comprising measuring the level of anti-MSP-3 IgG3 and/or IgG1 antibodies and the serum of said patient; and correlating a low level of said IgG3 and/or IgG1 anti-MSP-3 antibodies with the possibility that the patient may not be saved only by quinine treatment.  
     
     
         18 . A method for treating a cerebral malaria patient in need thereof, comprising administering to said patient anti-MSP-3 IgG3 or IgG1 antibodies.  
     
     
         19 . A method for treating a cerebral malaria patient in need thereof, comprising administering to said patient a pharmaceutical composition according to  claim 12 .  
     
     
         20 . A method for lowering the parasitemia in a malarial patient in need thereof, comprising administering to said patient anti-MSP-3 IgG3 or IgG1 antibodies or both.  
     
     
         21 . A method for lowering the parasitemia in a malarial patient in need thereof, comprising administering to said patient a pharmaceutical composition according to  claim 12 .  
     
     
         22 . The method of  claim 18  or  claim 20 , wherein said antibodies are directed against the MSP-3b peptide (SEQ ID No: 12), the MSP-3c peptide (SEQ ID No: 13), or the MSP-3d peptide (SEQ ID No: 14) or against several of these peptides.  
     
     
         23 . The method of  claim 20 , wherein said antibody is an IgG3.  
     
     
         24 . A kit for the in vitro control of a premunition state against malaria in an individual who has been immunized against it, comprising a native MSP-3 protein from  Plasmodium falciparum , a medium suitable for formation of an antigen-antibody complex, and reagents for detection of the antigen-antibody complex.