Recombinant protein containing a c-terminal fragment of plasmodium msp-1

Abstract

The invention relates to a recombinant protein fabricated in a baculovirus system, of which the essential constitutive polypeptide sequence is that of a C-terminal fragment of 19 kilodalton (p19) of the surface protein 1 (protein MSP-1) of the merozoite parasite of the Plasmodium type, particularly Plasmodium falciparum , which is infectious for humans, said C-terminal fragment remaining normally anchored at the surface of the parasite at the end of its penetration phase into human erythrocytes, in the occurrence of an infectious cycle. Said recombinant protein is applicable to the production of vaccines against malaria.

1 - 45 . (canceled) 
     
     
         46 . A vaccine composition comprising:
 1) a first recombinant protein comprising:   a) a 19 kilodalton (p19) C-terminal fragment of a surface protein 1 of a merozoite form (MSP-1) protein of a  Plasmodium falciparum  parasite, wherein said C-terminal fragment remains anchored via a glycosylphosphatidylinositol group to the surface of said  Plasmodium falciparum  parasite at an end of its penetration phase into human erythrocytes during an infectious cycle;   
       or
 b) a portion of said 19 kilodalton (p19) C-terminal fragment of a surface protein 1 of a merozoite form (MSP-1) protein, which can induce an immune response and which can inhibit parasitemia in vivo in a host infected with said  Plasmodium falciparum  parasite and contains at least one of the two epidermal growth factor (EGF) regions; and 
 2) a second recombinant p19 protein from a  Plasmodium  parasite that is homologous to  Plasmodium falciparum.    
 
     
     
         47 . The vaccine composition according to  claim 46 , wherein said first recombinant protein further comprises, upstream of said 19 kilodalton (p19) C-terminal fragment or fragment of said 19 kilodalton (p19) C-terminal fragment, a polypeptide containing less than 50 amino acids of a C-terminal end of p33 of a MSP-1 protein of a  Plasmodium  parasite. 
     
     
         48 . The vaccine composition according to  claim 46 , wherein said p19 C-terminal fragment or said portion of said p19 C-terminal fragment is deprived of an anchoring sequence of the native protein, which is normally implicated in the induction of anchoring the native protein to the cell membrane of a host in which it is expressed. 
     
     
         49 . The vaccine composition according to  claim 47 , wherein said polypeptide contains less than 35 amino acids. 
     
     
         50 . A vaccine composition according to  claim 46 , wherein the first recombinant protein is produced from a transformed insect cell deposited at the CNCM with registration number I-1661 or I-1662 on Feb. 1, 1996. 
     
     
         51 . The vaccinating composition according to  claim 46 , wherein said recombinant protein is conjugated to a carrier molecule. 
     
     
         52 . The vaccinating composition according to  claim 46 , further comprising a signal peptide, which is from a surface protein 1 of a merozoite form (MSP-1) of a  Plasmodium  parasite. 
     
     
         53 . The vaccinating composition according to  claim 52 , wherein said signal peptide is from  Plasmodium vivax.    
     
     
         54 . The vaccinating composition according to  claim 52 , wherein said signal peptide is from  Plasmodium falciparum.    
     
     
         55 . The vaccinating composition according to  claim 46 , wherein said second recombinant p19 protein from a  Plasmodium  parasite that is homologous to  Plasmodium falciparum  is from  Plasmodium vivax.    
     
     
         56 . The vaccinating composition according to  claim 46 , wherein said second recombinant p19 protein from a  Plasmodium  parasite that is homologous to  Plasmodium falciparum  is from  Plasmodium cynomolgi.    
     
     
         57 . The vaccinating composition according to  claim 46 , further comprising alum. 
     
     
         58 . The vaccinating composition according to  claim 52 , further comprising alum. 
     
     
         59 . A vaccinating composition which comprises:
 1) a first recombinant protein comprising:   a) a sequence comprising thirty-two amino acids of a surface protein 1 of a merozoite form (a MSP-1 protein) of a  Plasmodium vivax  from Met 1  to Asp 32 ; and   b) a 19 kilodalton C-terminal fragment of a surface protein 1 of a merozoite form (MSP-1) of  Plasmodium falciparum  comprising an amino acid sequence from Asn at amino acid position 3 to Ser at amino acid position 95 of SEQ ID NO: 1 or a 19 kilodalton C-terminal fragments of a surface protein 1 of a merozoite form (MSP-1) of  Plasmodium falciparum  comprising an amino acid sequence from Asn at amino acid position 3 to Ile at amino acid position 116 of SEQ ID NO: 4; and   2) a second recombinant p19 protein from a  Plasmodium  parasite that is homologous to  Plasmodium falciparum.      
     
     
         60 . The vaccine composition according to  claim 59 , wherein said second recombinant p19 protein parasite that is homologous to  Plasmodium falciparum  is from  Plasmodium vivax.    
     
     
         61 . A vaccinating composition which comprises:
 1) a first recombinant protein comprising:   a) a sequence comprising thirty-two amino acids of a surface protein 1 of a merozoite form (a MSP-1 protein) of a  Plasmodium vivax  from Met 1  to Asp 32 ; and   b) a 19 kilodalton C-terminal fragment of a surface protein 1 of a merozoite form (MSP-1) of  Plasmodium cynomolgi  comprising an amino acid sequence from Lys 276  to Ser 380  as shown in SEQ ID NO: 11 or a fragment thereof which can induce an immune response and which can inhibit parasitemia in vivo in a host infected with said  Plasmodium falciparum  parasite; and   2) a second recombinant p19 protein from a  Plasmodium  parasite that is homologous to  Plasmodium cynomolgi.      
     
     
         62 . The vaccine composition according to  claim 61 , wherein said second recombinant p19 protein parasite that is homologous to  Plasmodium cynomolgi  is from  Plasmodium vivax.    
     
     
         63 . The vaccine according to  claim 46 , wherein said portion of said p19 C-terminal fragment has a molecular eight of from 10 to 25 kDa. 
     
     
         64 . The vaccine according to  claim 46 , wherein said portion of said p19 C-terminal fragment has a molecular eight of from 10 to 15 kDa. 
     
     
         65 . The vaccine composition according to  claim 46 , wherein said second recombinant p19 protein is from  Plasmodium vivax  and wherein said vaccine composition further comprises:
 a) a p42 fragment from  Plasmodium falciparum , wherein said from  Plasmodium falciparum  is deprived of its most hypervariable regions, and   b) a p42 fragment from  Plasmodium vivax , wherein said from  Plasmodium vivax  is deprived of its most hypervariable regions.   
     
     
         66 . The vaccine composition according to  claim 65 , further comprising alum.