Table 1.

Shigella vaccine development strategies (past and present).

Live attenuated vaccines
Vaccine strain	Attenuation/mutation	Phase of development	Reference
Attenuated mutants obtained by serial passages in vitro
SmD in Yugoslavia	Serial passages in vitro	Phase III	Mel et al. [1971, 1974]
Istrati T32 in Romania	Serial passages in vitro	Phase III and IV	Meitert et al. [1984]
Hybrid live vector Shigella vaccine
Escherichia coli K12–Shigella flexneri 2a	Escherichia coli K12 vector of Shigella invasiveness plasmid; aroD	Phase IIb	Cohen et al. [1994];
Attenuated mutants obtained by recombinant DNA technology
S. flexneri 2a CVD 1208S	guaBA, sen, set	Phase II	Kotloff et al. [2007]
Shigella sonnei WRSs1	virG	Phase II	Orr et al. [2005]
S. sonnei WRSs2, WRSs3	virG, senA, senB, msbB2	Preclinical	Kotloff et al. [2002]; Barnoy et al. [2011]; Bedford et al. [2011]
S. flexneri 2a SC602	virG, iuc	Phase IIb	Sansonetti and Arondel [1991]; Coster et al. [1999]; Rahman et al. [2011]
S. flexneri 2a WRSf2G11, 12, 15	virG, senA, senB, msbB2	Preclinical	Ranallo et al. [2012]
Shigella dysenteriae 1 WRSd1	virG, stxAB	Phase I	McKenzie et al. [2006]
Inactivated vaccines	Vaccine candidate	Phase of development	Reference
Whole cell killed vaccines	S. flexneri 2a, 3a, S. sonnei	Preclinical	McKenzie et al. [2006]
Subunit vaccines
Chemical glycoconjugates	S. flexneri 2a, S. sonnei, PS- rec. exoprotein A	Preclinical and phases I, II and III	Cohen et al. [1997]; Ashkenazi et al. [1999]; Passwell et al. [2010]
Synthetic glycoconjugates	S. flexneri 2a synt O ag-tetanus toxoid	Preclinical	Pozsgay et al. [2007]; Phalipon et al. [2009]
Bioglycoconjugates	S. dysenteriae 1 LPS exoprotein A	Phase I	Fernandez et al. [2009]
Proteosomes LPS	S. flexneri 2a, S. sonnei	Phase II	Fries et al. [2001]
Ribosomes LPS	S. sonnei, S. flexneri	Preclinical	Levenson et al. [1995]; Shim et al. [2007]
Purified Ipa proteins	Shigella spp.	Preclinical	Martinez-Becerra et al. [2013]
GMMA protein vesicles	S. flexneri 2a, S. sonnei	Preclinical	Scorza et al. [2012]
Combined LPS and common proteins	S. flexneri 2a	Phase I	Oaks and Turbyfill [2006]; Riddle et al. [2011]

Ipa, invasion plasmid antigen; LPS, lipopolysaccharide; SmD, streptomycin dependent; GMMA, generalized modules of membrane antigens.