Plasmodium falciparum sporozoite and liver stage antigens

Abstract

The invention provides novel malaria polypeptides expressed at the pre-erythrocytic stage of the malaria life-cycle. The antigens can be utilized to induce an immune response against malaria in a mammal by administering the antigens in vaccine formulations or expressing the antigens in DNA or other nucleic acid expression systems delivered as a vaccine formulation.

1 . An immunogenic composition comprising one or more isolated polypeptides and a pharmaceutically acceptable carrier, wherein the isolated polypeptides comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, 10, 12 and 14, and immunogenic derivatives thereof. 
     
     
         2 . An immunogenic composition comprising one or more isolated nucleic acid molecules encoding one or more polypeptides, wherein said polypeptides are encoded by nucleic acid sequences selected form the groupo consisting of SEQ ID NOs: 1, 3, 5, 7, 9 11 and 13. 
     
     
         3 . The immunogenic composition of  claim 1 , wherein said polypeptides contain HLA class I epitopes. 
     
     
         4 . The immunogenic composition of  claim 2 , wherein said nucleic acid sequences contain one or more regions encoding an HLA class I epitope. 
     
     
         5 . The immunogenic composition of  claim 2 , wherein said nucleic acid sequences are inserted and the polypeptides are expressed from a DNA plasmid or viral expression system, wherein said viral expression systems are replicating or nonreplicating. 
     
     
         6 . The immunogenic composition of  claim 5 , wherein said viral expression system is selected from the group consisting of alphavirus replicon, adenovirus, poxvirus, adeno-associated virus, cytomegalovirus, canine distemper virus, yellow fever virus and retrovirus. 
     
     
         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  claim 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 isolated nucleic acid molecules encode contain HLA class I epitopes. 
     
     
         10 . 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 comprise a composition comprising one or more said isolated nucleic acid molecules, as in  claim 2 , inserted into a suitable expression vector, and wherein said boosting immunizations comprise a malaria polypeptide as in  claim 1  or comprises a composition comprising one or more isolated nucleic acid molecules, as in  claim 2 , inserted into suitable expression vector. 
     
     
         11 . 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. 
     
     
         12 . The method of  claim 10 , 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. 
     
     
         13 . The method of  10 , wherein said priming immunization vector is an alphavirus vector and said boosting immunization vector is nonalphavirus vector. 
     
     
         14 . The method of  claim 10 , wherein said priming immunization comprises an expression vector that is 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  claim 1 . 
     
     
         15 . The method of  claim 12 , wherein the alphavirus replicon preparation is selected from the group consisting of RNA replicons, DNA replicons and alphavirus replicon particles. 
     
     
         16 . The method of  claim 12 , wherein the alphavirus is selected from the group consisting of Venzuelean Equine Encephalitis Virus, Semliki Forest Virus and Sindbis Virus. 
     
     
         17 . The method of  claim 13 , wherein the non-alphavirus viral expression system is selected from the group consisting of poxvirus, adenovirus, adeno-associated virus and retrovirus. 
     
     
         18 . The method of  claim 17 , wherein the poxvirus is selected from the group consisting of cowpox, canarypox, vaccinia, modified vaccinia Ankara, or fowlpox.