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. Author manuscript; available in PMC: 2016 Nov 22.
Published in final edited form as: EcoSal Plus. 2016 Nov;7(1):10.1128/ecosalplus.ESP-0010-2016. doi: 10.1128/ecosalplus.ESP-0010-2016

Table 1.

Selected candidate live oral Salmonella vaccines against human disease tested in Phase 1/Phase 2 clinical trials.

Attenuation strategy Vaccine strain Serovar;
strain; relevant genotype		 Relevant phenotype Ref
Chemical
mutagenesis 		Ty21a Typhi;
Ty2; ΔrpoS ΔgalE ΔgalK ΔilvD
  ΔvexD 		Natural RpoS-dependent sensitivity to
environmental stressors; defective
synthesis of LPS; auxotrophic for
isoleucine and valine; defective synthesis
of Vi		 (69)
Engineered
deletions in
rpoS 		χ9639* Typhi;
Ty2; ΔrpoS 		Natural RpoS-dependent sensitivity to
environmental stressors		 (90)
χ9640* Typhi;
Ty2; rpoS+		 Engineered RpoS-mediated resistance to
environmental stressors		 (90)
χ9633* Typhi;
ISP1820; rpoS+ 		Natural RpoS-mediated resistance to
environmental stressors		 (90)
Engineered
deletions in
phoP/phoQ 		Ty800 Typhi;
Ty2; ΔrpoS ΔphoP ΔphoQ 		Natural RpoS-dependent sensitivity to
environmental stressors; defective in pH
and osmolarity induction of invasion
virulence factors		 (94)
Ty1033ǂ Typhi;
Ty2; ΔrpoS ΔphoP ΔphoQ 		Natural RpoS-dependent sensitivity to
environmental stressors; defective in pH
and osmolarity induction of invasion
virulence factors		 (96)
LH1160ǂ Typhimurium;
ATCC 14028; ΔphoP ΔphoQ 		Defective in pH and osmolarity induction
of invasion virulence factors		 (95)
Engineered
deletions in
ssaV 		M01ZH09 Typhi;
Ty2; ΔrpoS ΔaroC ΔssaV 		Natural RpoS-dependent sensitivity to
environmental stressors; auxotrophic for
aromatic amino acids; defective for proper
secretion of SPI-2 effector proteins		 (97)
(99,
100)
(101)
(102)
WT05 Typhimurium;
TML; ΔaroC ΔssaV 		Auxotrophic for aromatic amino acids;
defective for proper secretion of SPI-2
effector proteins		 (97)
Engineered
deletions in
aroC, aroD,
and htrA 		CVD 908 Typhi;
Ty2; ΔrpoS ΔaroC ΔaroD 		Natural RpoS-dependent sensitivity to
environmental stressors; auxotrophic for
aromatic amino acids		 (105)
CVD 908-
htrA 		Typhi;
Ty2; ΔrpoS ΔaroC ΔaroD ΔhtrA 		Natural RpoS-dependent sensitivity to
environmental stressors; auxotrophic for
aromatic amino acids; sensitive to
environmental heat shock		 (107)
CVD 909 Typhi;
Ty2; ΔrpoS Ptac-tviA ΔaroC ΔaroD
  ΔhtrA 		Natural RpoS-dependent sensitivity to
environmental stressors; constitutive
expression of TviA regulator and Vi
antigen; auxotrophic for aromatic amino
acids; sensitive to environmental heat
shock		 (77)
(108)
(110)
*

These vaccines were engineered as live vector vaccines, carrying additional chromosomal mutations, as well as also carrying multicopy plasmids expressing a pneumococcal foreign antigen. However, all candidate vaccines carried the same attenuating lesions and differed only with respect to parental strain used (Ty2 vs ISP1820) and the presence of rpoS.

ǂ

These vaccines were engineered as live vector vaccines, carrying one additional chromosomal deletion in the purB gene, as well as also carrying multicopy plasmids encoding both purB and the foreign antigen urease from Helicobacter pylori. However, both S. Typhi and S. Typhimurium candidate vaccines were isogenic for the attenuating lesions tested in clinical trials.