Malaria vaccine

Abstract

The present invention provides a particle comprising a polypeptide and at least one malaria antigen, and a composition or vaccine comprising thereof, its use in medicine, particularly in the prevention or treatment of malaria infections.

1 - 44 . (canceled) 
     
     
         45 . A virus-like particle comprising a virus structural polypeptide and at least one malaria antigen,
 wherein said virus structural polypeptide is a polypeptide derived from alphavirus or flavivirus.   
     
     
         46 . The virus-like particle according to  claim 45 , wherein said virus structural polypeptide is a polypeptide derived from alphavirus. 
     
     
         47 . The virus-like particle according to  claim 45 , wherein said virus structural polypeptide comprises the capsid and/or the envelope proteins E1 and E2. 
     
     
         48 . The virus-like particle according to  claim 47 , wherein said at least one malaria antigen is inserted into E2 of the envelope protein. 
     
     
         49 . The virus-like particle according to  claim 45 , wherein said virus structural polypeptide is a polypeptide derived from Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV). 
     
     
         50 . The virus-like particle according to  claim 45 , wherein said at least one malaria antigen is a fragment derived from the circumsporozoite protein. 
     
     
         51 . The virus-like particle according to  claim 45 , wherein said at least one malaria antigen is an antigen comprising (NPNA) n  wherein n is from 4 to 30 and/or an antigen comprising (EYLNKIQSLSTEWSPCSVT) y  wherein y is from 1 to 6. 
     
     
         52 . The virus-like particle according to  claim 49 , wherein said at least one malaria antigen is inserted between 509-510, 510-511, 511-512, 519-520, 529-530, 530-531 or 531-532 of SEQ ID NO: 1 or 2, or between residues 515-516, 516-517, 517-518, 518-519, 519-520, 536-537, 537-538 or 538-539 of SEQ ID NO: 3. 
     
     
         53 . The virus-like particle according to  claim 49 , wherein the particle is Chikungunya virus-like particle consisting of one or more envelope protein E2 into which the antigen is inserted, one or more envelope protein E1 and one or more capsid, and
 wherein the envelope protein E2 into which the antigen is inserted consists of an amino acid sequence represented by SEQ ID NO: 50; the envelope protein E1 consists of an amino acid sequence represented by SEQ ID NO: 51; and the capsid consists of an amino acid sequence represented by SEQ ID NO: 52.   
     
     
         54 . The virus-like particle according to  claim 49 , wherein the particle is Venezuelan equine encephalitis virus-like particle consisting of one or more envelope protein E2 into which the antigen is inserted, one or more envelope protein E1 and one or more capsid, and
 wherein the envelope protein E2 into which the antigen is inserted consists of an amino acid sequence represented by SEQ ID NO: 53; the envelope protein E1 consists of an amino acid sequence represented by SEQ ID NO: 54; and the capsid consists of an amino acid sequence represented by SEQ ID NO: 55.   
     
     
         55 . An isolated nucleic acid molecule comprising a nucleotide sequence for expressing the particle according to  claim 45 . 
     
     
         56 . A vector comprising the nucleic acid molecule according to  claim 55 , wherein the vector optionally comprises an expression control sequence operably linked to the nucleic acid molecule. 
     
     
         57 . A pharmaceutical composition comprising:
 (a) the virus-like particle according to  claim 45  and/or a nucleic acid molecule comprising a nucleotide sequence for expressing the particle according to  claim 45 ; and   (b) a pharmaceutically acceptable carrier.   
     
     
         58 . A vaccine composition comprising the virus-like particle according to  claim 45 . 
     
     
         59 . A method of treating malaria in a mammal, comprising administering an effective amount of the virus-like particle according to  claim 45  and/or a nucleic acid molecule comprising a nucleotide sequence for expressing the particle according to  claim 45  to the mammal in need thereof. 
     
     
         60 . A method of treating malaria in a mammal, comprising administering
 a priming composition comprising at least one first malaria antigen or at least one polynucleotide encoding at least one first malaria antigen; and   a boosting composition comprising at least one polypeptide comprising at least one second malaria antigen or at least one polynucleotide encoding at least one second malaria antigen,   wherein at least one of said compositions comprises the virus-like particle according to  claim 45  and/or a nucleic acid molecule comprising a nucleotide sequence for expressing the particle according to  claim 45  to the mammal in need thereof.   
     
     
         61 . The method according to  claim 60 , wherein the polynucleotide encodes substantially all of the circumsporozoite protein. 
     
     
         62 . The vaccine composition according to  claim 58  for use in the prevention or treatment of malaria, comprising a plurality of malaria-derived antigens. 
     
     
         63 . A kit comprising
 (a) a vaccine composition comprising the virus-like particle according to  claim 45 ; and   (b) another vaccine composition comprising the virus-like particle according to  claim 45 ,   wherein the particle contained in (a) is a virus-like particle which is different from the particle contained in (b).   
     
     
         64 . The kit according to  claim 63 , further comprising
 (c) a third vaccine composition comprising a virus-like comprising a virus structural polypeptide and at least one malaria antigen, wherein said virus structural polypeptide is a polypeptide derived from alphavirus or flavivirus,
 wherein said first vaccine composition is used for priming immunization and said second and third vaccine compositions are used for boosting immunization, and 
 wherein the virus-like particle contained in said third vaccine composition is different from the virus-like particle contained in said first and second vaccine compositions, or is the same as a virus-like particle contained in either said first or second vaccine composition.