Plasmodium falciparum antigens

Abstract

The invention relates to antigens, associated with sterile immunity, and methods of their use, in an immunogenic formulation to confer an immune response against Plasmodium falciparum . The inventive antigens were identified by their association with sterile immunity against malaria.

What is claimed is: 
     
         1 . An immunogenic composition comprising a nucleic acid sequence expressed by a suitable expression system, wherein said nucleic acid sequence expresses an isolated protein expressed by  Plasmodium falciparum  sporozoites encoded by one or more of the locus selected from the group consisting of PF10925w, PF14_0051, PFL2140c, PFE1085w, and PF13_0222, wherein the isolated protein has the amino acid sequence selected from the group consisting of SEQ ID No. 2, 6, 24, 28, and 36, and wherein said isolated protein is expressed from a nucleotide sequence, inserted into a suitable expression vector capable of protein expression in a mammal, wherein the nucleotide sequence comprises the nucleotide sequence selected from the group consisting of SEQ ID No. 1, 5, 23, 27, and 35, wherein said suitable expression vector is a DNA plasmid or replicating or nonreplicating viral vector. 
     
     
         2 . The immunogenic composition of  claim 1 , wherein the composition also comprises a nucleic acid sequence expressed by a suitable expression system, wherein said nucleic acid sequence expresses isolated proteins expressed by  Plasmodium falciparum  sporozoites encoded by one or more of the loci selected from the group consisting of PFB0285c, PFL1620w, PF10_0211, PFB0150c, PF11_0344, PFE0060w, PF08_0034, PF08_0054, PFC0210c, PF11_0404, PF13_0201, PFL2505c, PF13_0222, and MAL13P1.22, wherein the isolated proteins have the amino acid sequences selected from the group consisting of, with the amino acid sequences of SEQ ID No. 4, SEQ ID No. 10, SEQ ID No. 12, SEQ ID No. 14, SEQ ID No. 16, SEQ ID No. 18, SEQ ID No. 20, SEQ ID No. 22, SEQ ID 26, SEQ ID No. 30, SEQ ID No. 32, SEQ ID No. 34, and SEQ ID No. 38, wherein the one or more isolated proteins are encoded by one or more the nucleic acid sequences of SEQ ID No. 3, SEQ ID No. 9, SEQ ID No. 11, SEQ ID No. 13, SEQ ID No. 15, SEQ ID No. 17, SEQ ID No. 19, SEQ ID No. 21, SEQ ID 25, SEQ ID No. 29, SEQ ID No. 31, SEQ ID No. 33, and SEQ ID No. 37 and inserted into and expressed from a suitable expression system, wherein said suitable expression vector is a DNA plasmid or replicating or nonreplicating viral vector. 
     
     
         3 . The immunogenic composition of  claim 1 , wherein said viral vector is selected from the group consisting of DNA plasmid, alphavirus replicon, adenovirus, poxvirus, adeno-associated virus, cytomegalovirus, canine distemper virus, yellow fever virus and retrovirus. 
     
     
         4 . The immunogenic composition of  claim 3 , wherein the alphavirus replicon preparation is selected from the group consisting of RNA replicons, DNA replicons and alphavirus replicon particles. 
     
     
         5 . The immunogenic composition of  claim 4 , wherein the alphavirus is selected from the group consisting of Venzuelean Equine Encephalitis Virus, Semliki Forest Virus and Sindbis Virus. 
     
     
         6 . The immunogenic composition of  claim 3 , wherein the poxvirus is selected from the group consisting of cowpox, canarypox, vaccinia, modified vaccinia Ankara, or fowlpox. 
     
     
         7 . A method of inducing an immune response against malaria in a mammal, which method comprises administering to a mammal a composition comprising one or more isolated nucleic acid molecules, inserted into a suitable expression vector, encoding isolated malaria polypeptides, wherein said isolated nucleic acid molecules are as in  claims 1  or  2 . 
     
     
         8 . The method of  claim 7 , where the suitable expression system is a DNA plasmid or replicating or nonreplicating viral vector. 
     
     
         9 . The method of  claim 7 , wherein said method further comprises one or more priming and one or more boosting immunizations, wherein said priming immunizations comprise one or more malaria polypeptides, as in  claim 1  or  2 , inserted into a suitable expression vector, and wherein said boosting immunizations comprise a malaria polypeptide, as in  claim 1  or  2 , inserted into suitable expression vector. 
     
     
         10 . The method of  claim 7 , wherein said suitable expression vector is selected from the group consisting of DNA plasmid alphavirus replicon, adenovirus, poxvirus, adenoassociated virus, cytomegalovirus, canine distemper virus, yellow fever virus and retrovirus. 
     
     
         11 . The method of  claim 9 , wherein said priming immunization vector is an alphavirus vector and said boosting immunization vector is nonalphavirus vector. 
     
     
         12 . The method of  claim 9 , wherein said priming immunization comprises an expression vector that is a DNA plasmid or an adenovirus and the boosting immunization is selected from the group consisting of adenovirus, adenovirus heterologous to the priming adenovirus, poxvirus and polypeptide, wherein said polypeptides have amino acid sequences as in  claims 1  or  2 . 
     
     
         13 . The method of  claim 10 , wherein the alphavirus replicon is selected from the group consisting of RNA replicons, DNA replicons and alphavirus replicon particles. 
     
     
         14 . The method of  claim 11 , wherein the non-alphavirus viral is selected from the group consisting of poxvirus, adenovirus, adeno-associated virus and retrovirus. 
     
     
         15 . The method of  claim 13 , wherein the alphavirus is selected from the group consisting of Venzuelean Equine Encephalitis Virus, Semliki Forest Virus and Sindbis Virus. 
     
     
         16 . The method of  claim 14 , wherein the poxvirus is selected from the group consisting of cowpox, canarypox, vaccinia, modified vaccinia Ankara, or fowlpox.