TABLE 1.
Recombinant Salmonella strains for human vaccines
| Vaccine strategy | Target serovar(s) | Vaccine or strain name | Genetic modification | Phase | Reference |
|---|---|---|---|---|---|
| Live-attenuated Salmonella vaccines | Salmonella Typhi | CVD 908 | Salmonella Typhi Ty2; ΔaroC, ΔaroD | Phase 1 | (23) |
| CVD 908-htrA | Salmonella Typhi Ty2; ΔaroC, ΔaroD ΔhtrA | Phase 2 | (24–26) | ||
| CVD 909 | Salmonella Typhi Ty2; ΔaroC, ΔaroD, ΔrpoS Ptac-tviA, ΔhtrA | Phase 2 | (27) | ||
| χ4073 | Salmonella Typhi Ty2; Δcya Δcrp Δcdt | Phase 1 | (28) | ||
| Ty800 | Salmonella Typhi Ty2; ΔphoP ΔphoQ | Phase 1 | (29) | ||
| M01ZH09 | Salmonella Typhi Ty2; ΔaroC ΔssaV | Phase1/2 | (30, 31) | ||
| Salmonella Paratyphi A | CVD 1902 | ATCC 9150; ΔguaBA ΔclpX | Phase 1 | (32, 33) | |
| Salmonella Paratyphi B | CVD 2005 | CMF 6999; ΔguaBA ΔclpX | Pre-clinical | (34) | |
| Salmonella Typhimurium | WT05 | TML; ΔaroC ΔssaV | Phase 1 | (35) | |
| LH1160 | ATCC 14028; ∆purB ∆phoP/Q | Phase 1 | (36) | ||
| CVD 1931 | D65; ΔguaBA ΔclpX | Pre-clinical | (37) | ||
| Salmonella Enteritidis | CVD 1944 | Salmonella Enteritidis R11; ΔguaBA ΔclpX | Pre-clinical | (37) | |
| Salmonella Newport | CVD 1966 | Salmonella Newport; ΔguaBA ΔhtrA | Pre-clinical | (38) | |
| Live-vector vaccines—expression from plasmids | Helicobacter pylori | Ty21a (pDB1) | Salmonella Typhi Ty21a; ΔthyA; expresses H. pylori Urease A and B antigens from thyA-stabilized expression plasmids | Phase 1 | (39, 40) |
| Streptococcus pneumoniae | χ9640 (pYA4088) | Salmonella Typhi Ty2 RpoS+; ΔPcrp527::TT araC PBAD crp, ΔPfur81::TT araC PBAD fur, Δpmi-2426, Δ(gmd-fcl)−26, ΔrelA198::araC PBAD lacI TT, ΔsopB1925, ΔagfBAC811, ΔtviABCDE10, ΔaraE25, and ΔasdA33; expresses S. pneumoniae surface protein antigen PspA from Asd+ expression plasmid | Phase 1 | (41) | |
| Live-vector vaccines—expression from the chromosome |
Salmonella Typhi and S. sonnei |
Ty21a-Ss (MD77) | Salmonella Typhi Ty21a expressing S. sonnei O-antigen genes integrated into tviD-vexA locus on the chromosome | Pre-clinical | (42) |
|
Salmonella Typhi and S. dysenteriae |
Ty21a-Sd (MD149) | Salmonella Typhi Ty21a expressing S. dysenteriae serotype 1 O-antigen genes integrated into tviD-vexA locus on the chromosome | Pre-clinical | (43) | |
| Salmonella Typhi and S. flexneri | Ty21a-2a (MD194) | Salmonella Typhi Ty21a expressing S. flexneri 2a O-antigen genes integrated into tviD-vexA locus on the chromosome | Pre-clinical | (44) | |
| Ty21a-3a (MD196)D | Salmonella Typhi Ty21a expressing S. flexneri 3a O-antigen genes integrated into tviD-vexA locus on the chromosome | Pre-clinical | (44) | ||
| Salmonella Typhimurium and Salmonella Enteritidis | S1075 | Salmonella Typhimurium S100; (Δabe:prt-tyvD1 Δcrp Δcya) (O9); chromosomal deletion–insertion mutations resulting in O-serotype conversion | Pre-clinical | (45) | |
| Salmonella Typhimurium and Salmonella Choleraesuis | S1157 | Salmonella Typhimurium S100; [Δ(rmlB-wbaP):(wzyC1-wzxC1) Δcrp Δcya] (O7); chromosomal deletion–insertion mutations resulting in O-serotype conversion | Pre-clinical | (45) | |
| Salmonella Typhi, Salmonella Typhimurium, and Salmonella Enteritidis | S1163 | Salmonella Typhimurium S100; (O9, Vi+ , ΔPtviA::PssaG Δcya Δcrp); chromosomal deletion–insertion mutations resulting in O-serotype conversion | Pre-clinical | (46) | |
| Live-vector vaccines mediating directed antigen delivery | S. aureus | MvP728 (p3635) |
Salmonella Typhimurium NCTC 12023 ΔhtrA ΔpurD (carrier strain MvP728); pWSK29 PsseA sseJ::lisA51-363::HA (p3635); T3SS effector protein SseJ fused with Listeria monocytogenes LisA |
Pre-clinical | (47) |
| N19 | Salmonella Typhimurium (ΔaroA ΔpryF) carrying PagC-invB-sipA-SaEsxA (ColE1 ori) | Pre-clinical | (48) | ||
| N20 | Salmonella Typhimurium (ΔaroA ΔpryF) carrying PagC-invB-sipA-SaEsxB (ColE1 ori) | Pre-clinical | (48) | ||
| P. aeruginosa | SV9699 | Salmonella Typhimurium 14028 aroA551::Tn10 ΔaroB::KmR; pWSK29-PsseA-SseJ-PcrV-FLAG (pIZ2267); T3SS effector protein SseJ fused with P. aeruginosa antigen PcrV | Pre-clinical | (49) | |
| Designed to cause regulated delayed lysis | Streptococcus pneumoniae | χ8937 (pYA3685) | Salmonella Typhimurium UK‐1 ΔasdA19::araC PBAD c2 ΔP murA7 ::araC PBAD murA Δ(gmd‐fcl)‐26; Expression plasmid pYA3685 releases pneumococcal surface protein A (PspA) within the lymphoid tissues. | Pre-clinical | (50) |
| M. tuberculosis | RASV χ11021 | Salmonella Typhimurium ΔPmurA25::TT araC PBADmurA ΔasdA27::TT araC PBAD c2 ΔaraBAD23 Δ(gmd-fcl)−26 Δpmi-2426 Δ relA198::TT araC PBAD lacI; Asd+/MurA+ lysis vector expresses M. tuberculosis proteins Ag85A294. | Pre-clinical | (51) | |
| Extraintestinal pathogenic E. coli | χ9558 (pYA4428) |
Salmonella Typhimurium strain UK-1 (χ3761);Δpmi-2426 Δ(gmd-fcl)−26 ΔPfur81:TT araC PBAD
furΔPcrp527:TT araC PBAD crp ΔasdA27:TT araC PBAD c2 ΔaraE25 ΔaraBAD23 ΔrelA198:araC PBAD lacI TT ΔsopB1925 ΔagfBAC811; expresses E. coli EcpA and EcpD recombinant antigens |
Pre-clinical | (52) | |
| Reagent strains for parenteral vaccines |
Salmonella Typhimurium and Salmonella Enteritidis |
CVD 1925 (pSEC10‐wzzB) and CVD 1943 | Salmonella Typhimurium I77 ΔguaBA ΔclpP ΔfliD ΔfljB (pSEC10-wzzB); Salmonella Enteritidis R11 ΔguaBA ΔclpP ΔfliD; OPS and flagellin for conjugate vaccines | Phase 2 | (53, 54) |
| STmG and SEnG | Salmonella Typhimurium 1418 tolR::aph; Salmonella Enteritidis 618 tolR::aph for production of GMMA | Phase1/2 | (55) |