Baculovirus produced Plasmodium falciparum vaccine

Abstract

Compositions and methods are provided for the induction of a protective immunize response in primates against a lethal challenge of Plasmodium.

What we claim is:  
     
         1 . An isolated p42-M nucleic acid encoding a p42 polypeptide wherein said p42-M nucleic acid is derived from a p42 nucleic acid by modifying one or more codons of said p42 nucleic acid such that said one or more modified codons are preferentially recognized by an insect cell expression system thereby resulting in increased translation of the mRNA transcribed from said p42-M nucleic acid.  
     
     
         2 . An isolated p42-M.2 nucleic acid wherein said nucleic acid encodes a p42 polypeptide wherein the codons encoding the carboxy-terminal histidine tail of p42 or p42-M have been removed.  
     
     
         3 . The isolated p42-M.2 nucleic acid of  claim 2  comprising nucleotide sequences from 1 through about 1200 of SEQ ID NO:17.  
     
     
         4 . The isolated p42-M nucleic acid of  claim 1  wherein said insect cell expression system comprises a  Trichoplusia ni  cell.  
     
     
         5 . A baculovirus vector comprising the p42-M or p42-M.2 nucleic acids of claims  1  or  2 .  
     
     
         6 . The baculovirus vector of  claim 5  wherein said p42-M or p42-M .2 nucleic acid comprises an optimized promoter.  
     
     
         7 . An isolated p42-M polypeptide wherein said polypeptide is encoded by a nucleic acid sequence comprising sequences from one 1 through about 1232 of SEQ ID NO: 6.  
     
     
         8 . The isolated p42-M polypeptide of  claim 7  comprising amino acid sequences from 1 through about 402 of SEQ ID NO:16.  
     
     
         9 . An isolated p42-M.2 polypeptide wherein the carboxy-terminal histidine tail of p42 or p42-M polypeptide has been removed.  
     
     
         10 . The isolated polypeptide of  claim 9  comprising amino acids from 1 through about 392 of SEQ ID NO:18.  
     
     
         11 . A pharmaceutical composition for treating plasmodium parasatemia in a mammal comprising the isolated p42 peptide of claims  7 ,  8 ,  9  or  10 .  
     
     
         12 . The pharmaceutical composition of  claim 11  further comprising an adjuvant selected from the group consisting QS-21 and ISA51 and mixtures thereof.  
     
     
         13 . The pharmaceutical composition of  claim 11  wherein said isolated p42 polypeptide is expressed in an insect cell and is more immunogenic in a mammalian host than is the same polypeptide expressed in yeast.  
     
     
         14 . The pharmaceutical composition of  claim 11 , wherein said isolated p42 polypeptide is from  Plasmodium falciparum.    
     
     
         15 . The pharmaceutical composition of  claim 11 , wherein said  Plasmodium falciparum  polypeptide is an allelic form selected from the group consisting of MAD, K1, and Wellcome isolates.  
     
     
         16 . The pharmaceutical composition of  claim 11 , wherein the transmembrane domain of said isolated p42 polypeptide is deleted.  
     
     
         17 . An anti-plasmodium vaccine comprising the isolated p42 polypeptide of claims  7 ,  8 ,  9 , or  10 .  
     
     
         18 . The anti-plasmodium vaccine of  claim 17  further comprising an adjuvant selected from the group consisting QS-21 and ISA51 and mixtures thereof.  
     
     
         19 . The anti-plasmodium vaccine of  claim 17  wherein said isolated p42 polypeptide is expressed in an insect cell and is more immunogenic in a mammalian host than is the same polypeptide expressed in yeast.  
     
     
         20 . A method of inducing an anti-plasmodium immune response in a mammal comprising administering to said mammal the vaccine of  claim 17 .  
     
     
         21 . The method of  claim 20 , wherein said immune response substantially reduces plasmodium parasitemia in said mammal.  
     
     
         22 . The method of  claim 21 , wherein said mammal is a primate.