Malaria vaccine and methods for producing same

Abstract

The present description relates to malaria vaccines comprising Plasmodium falciparum (Pf) polypeptide complexes and methods of producing the same. The Pf polypeptides in complexes or in a partially complexed arrangement may comprise two or more of the following polypeptides: PfRipr, PfCyrPa and PfRh5. Drosophila cells and expression vectors are also described.

1 .- 24 . (canceled) 
     
     
         25 . A  Drosophila  derived cell modified to express a  Plasmodium falciparum  (Pf) Ripr polypeptide from a heterologous polynucleotide encoding a PfRipr polypeptide and a suitable signal sequence, further comprising a heterologous polynucleotide encoding PfRh5 polypeptide and a suitable signal sequence, wherein each polynucleotide is operably linked to an expression control sequence which induces the Pf polypeptide expression in the cell and wherein the PfRipr polypeptide and the PfRh5 polypeptide from said cell induce merozoite invasion inhibitory antibodies when administered to a subject. 
     
     
         26 . The cell of  claim 25 , wherein co-expression of PfRipr and PfRh5 polypeptides in the cell induces increased yields of either or both polypeptides compared to mono-expression of either polypeptide. 
     
     
         27 . The cell of  claim 25 , further comprising a heterologous polynucleotide encoding a PfCyrPa polypeptide and a suitable signal sequence, operably linked to an expression control sequence which induces PfCyrPa polypeptide expression in the cell, wherein the PfRipr polypeptide, PfRh5 polypeptide and PfCyrPa polypeptide from said cell induce parasite invasion inhibitory antibodies when administered to a subject. 
     
     
         28 . The cell of  claim 25 , further comprising a heterologous polynucleotide encoding a PfEBA175 polypeptide and a suitable signal sequence, operably linked to a promoter which induces EBA175 polypeptide expression in the cell. 
     
     
         29 . The cell of  claim 27 , further comprising a heterologous polynucleotide encoding a PfEBA175 polypeptide and a suitable signal sequence, operably linked to a promoter which induces EBA175 polypeptide expression in the cell. 
     
     
         30 . A  Drosophila  cell comprising an expression vector comprising a polynucleotide encoding PfRipr polypeptide and a suitable signal sequence and an expression vector comprising a polynucleotide encoding PfRh5 polypeptide and a suitable signal sequence, wherein each polynucleotide is operably linked to an expression control sequence which induces Pf Ripr and PfRh5 polypeptide expression in a  Drosophila  derived cell, wherein the PfRipr polypeptide and the PfRh5 polypeptide from the cell induces parasite growth inhibitory antibodies when administered to a subject. 
     
     
         31 . A  Drosophila  cell of  claim 30  further comprising an expression vector comprising a polynucleotide encoding a PfCyrPa polypeptide and a suitable signal sequence, said polynucleotide operably linked to an expression control sequence which induces PfCyrPa polypeptide expression in a  Drosophila  derived cell, wherein the PfCyrPa polypeptide from said cell induces parasite growth inhibitory antibodies when administered to a subject. 
     
     
         32 . An expression vector comprising a polynucleotide encoding PfRipr polypeptide and a suitable signal sequence and a polynucleotide encoding PfRh5 polypeptide and a suitable signal sequence, wherein each polynucleotide is operably linked to an expression control sequence which induces PfRipr and PfRh5 polypeptide expression in a  Drosophila  derived cell, wherein the PfRipr polypeptide and the PfRh5 polypeptide from the cell induces parasite growth inhibitory antibodies when administered to a subject. 
     
     
         33 . A  Drosophila  cell comprising the expression vector of  claim 32 . 
     
     
         34 . A  Drosophila  cell comprising the expression vector of  claim 32  and further comprising an expression vector comprising a polynucleotide encoding a PfCyrPa polypeptide and a suitable signal sequence, said polynucleotide operably linked to an expression control sequence which induces PfCyrPa polypeptide expression in a  Drosophila  derived cell, wherein the PfCyrPa polypeptide from said cell induces parasite growth inhibitory antibodies when administered to a subject. 
     
     
         35 . An immunogenic composition comprising an expression vector comprising a polynucleotide encoding PfRipr polypeptide and a suitable signal sequence and an expression vector comprising a polynucleotide encoding PfRh5 polypeptide and a suitable signal sequence, wherein each polynucleotide is operably linked to an expression control sequence which induces PfRipr and PfRh5 polypeptide expression, and a physiologically or pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         36 . The immunogenic composition of  claim 35 , further comprising an expression vector comprising a polynucleotide encoding a PfCyrPa polypeptide and a suitable signal sequence, said polynucleotide operably linked to an expression control sequence which induces PfCyrPa polypeptide expression, and a physiologically or pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         37 . The immunogenic composition of  claim 35  further comprising an adjuvant. 
     
     
         38 . The immunogenic composition of  claim 36  further comprising an adjuvant. 
     
     
         39 . An immunogenic composition comprising the vector of  claim 32  and a physiologically or pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         40 . The immunogenic composition of  claim 39  further comprising an adjuvant. 
     
     
         41 . A method of producing PfRipr and PfRh5 polypeptide comprising transfecting a  Drosophila  cell with a vector of  claim 32  and isolating PfRipr and PfRh5 polypeptide from said cells. 
     
     
         42 . A Pf protein complex or Pf protein mixture purified from the cell of  claim 25 .