Broad spectrum vaccine against typhoidal and non-typhoidal
The present invention is drawn to multivalent Salmonella enterica serovar conjugate vaccines comprising conjugates of S. Typhimurium, S. Enteritidis, S. Choleraesuis, S. Typhi, S. Paratyphi A and optionally S. Paratyphi B, wherein the conjugates comprise a hapten antigen and a carrier antigen, wherein at least one of the hapten antigens or carrier antigens is characteristic of the Salmonella enterica serovar. The present invention also provides Salmonella enterica serovar reagent strains to produce the multivalent conjugate vaccines and attenuated Salmonella enterica serovars for use as vaccines.
1. A method of inducing an immune response, comprising administering to a subject in need thereof an immunologically-effective amount of a composition comprising
1) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Typhimurium wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S. Enteritidis, S. Choleraesuis, S. Typhi and S . Paratyphi A and combinations thereof;
2) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S. Enteritidis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof;
3) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S. Choleraesuis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S. Typhi and S. Paratyphi A and combinations thereof;
4) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S. Typhi wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof; and
5) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Paratyphi A wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof.
2. The method of claim 1 , wherein the composition further comprises a S . Paratyphi B conjugate comprising core-O polysaccharide (COPS) linked to a phase 1 flagella protein (FliC).
3. A composition comprising
1) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Typhimurium wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof;
2) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S. Enteritidis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof;
3) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Choleraesuis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof;
4) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Typhi wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof; and
5) a conjugate comprising a phase 1 flagella protein from the Salmonella enterica serovar S . Paratyphi A wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from a Salmonella enterica serovar selected from the group consisting of S . Typhimurium, S . Enteritidis, S . Choleraesuis, S . Typhi and S . Paratyphi A and combinations thereof.
4. The composition of claim 3 , further comprising a S . Paratyphi B conjugate comprising core-O polysaccharide (OPS) linked to a phase 1 flagella protein.
5. The composition of claim 3 , wherein the phase 1 flagella protein of parts 1-5 )is FliC.
6. The composition of claim 3 , wherein the conjugate of part 1) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Typhimurium wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Typhimurium.
7. The composition of claim 3 , wherein the conjugate of part 2) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Enteritidis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Enteritidis.
8. The composition of claim 3 , wherein the conjugate of part 3) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Choleraesuis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Choleraesuis.
9. The composition of claim 3 , wherein the conjugate of part 4) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Typhi wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Typhi.
10. The composition of claim 3 , wherein the conjugate of part 5) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Paratyphi A wherein the phase 1 flagella protein is FliC or FliC FI411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Paratyphi A.
11. The composition of claim 3 ,
wherein the conjugate of part 1) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Typhimurium wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S. Typhimurium,
wherein the conjugate of part 2) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Enteritidis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Enteritidis,
wherein the conjugate of part 3) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Choleraesuis wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Choleraesuis,
wherein the conjugate of part 4) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Typhi wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Typhi,
wherein the conjugate of part 5) comprises a phase 1 flagella protein from the Salmonella enterica serovar S . Paratyphi A wherein the phase 1 flagella protein is FliC or FliC I411A and a core-O polysaccharide, wherein the core-O polysaccharide is from S . Paratyphi A.
12. The composition of claim 11 , wherein the phase 1 flagella protein of parts 1-5) is FliC.
13. The composition of claim 11 , wherein the phase 1 flagella protein of parts 1-5) is FliC I411A.