Broad spectrum conjugate vaccine to prevent klebsiella pneumoniae and pseudomonas aeruginosa infections
The present invention is drawn to conjugates and vaccine compositions comprising a Pseudomonas flagellin or an antigenic fragment or derivative thereof linked to one or more Klebsiella surface polysaccharide antigens, such as Klebsiella pneumoniae O polysaccharide from serovars O1, O2 a , O2 a,c , O3, O4, O5, O7, O8 and O12. The present invention also provides serovar reagent strains to produce the conjugates and vaccine compositions and methods of inducing an immune response with the conjugates and vaccine compositions.
1. A conjugate comprising a Klebsiella pneumoniae surface polysaccharide antigen and a Pseudomonas aeruginosa flagellin protein or antigenic fragment thereof, wherein the conjugate comprises i) Pseudomonas aeruginosa flagellin type A (FlaA) or an antigenic fragment thereof and/or Pseudomonas aeruginosa flagellin type B (FlaB) or an antigenic fragment thereof and ii) OPS from Klebsiella pneumoniae selected from the group consisting of Klebsiella pneumoniae serovars 01, 02a, 03, 05.
2. The conjugate of claim 1 , wherein the surface polysaccharide antigen and the flagellin are covalently linked.
3. The conjugate of claim 1 , wherein Pseudomonas flagellin is covalently linked to one or more OPS from a single Klebsiella pneumoniae serovar type.
4. The conjugate of claim 1 , wherein the Pseudomonas aeruginosa flagellin type A (FlaA) comprises SEQ ID NO: 1.
5. The conjugate of claim 1 , wherein the Pseudomonas aeruginosa flagellin type B (FlaB) comprises SEQ ID NO: 2.
6. A vaccine composition comprising one or more conjugates of claim 1 .
7. The vaccine composition of claim 6 , wherein the composition is a multivalent conjugate vaccine comprising one or more Pseudomonas flagellins covalently linked to one or more Klebsiella O polysaccharides (OPS).
8. The vaccine composition of claim 6 , wherein the conjugate vaccine is a multivalent conjugate vaccine comprising two different Pseudomonas flagellin or an antigenic fragment thereof covalently linked to one or more Klebsiella O polysaccharides (OPS).
9. The vaccine composition of claim 8 , wherein the multivalent conjugate vaccine comprises four different OPS antigens from Klebsiella pneumoniae serovars 01, O2a, 03, and 05.
10. A method of making the conjugate of claim 1 , comprising covalently bonding a Klebsiella pneumoniae surface polysaccharide antigen and a Pseudomonas aeruginosa flagellin protein or an antigenic fragment thereof.
11. The method of claim 10 , wherein the Klebsiella pneumoniae has an attenuating mutation in the guaBA locus and a mutation in the wza-wzc locus.