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. 2021 Jan 8;11:579907. doi: 10.3389/fimmu.2020.579907

Table 1.

Lig Vaccine Studies.

Publication Immunization Challenge Survival** P value
1st Author, Year Antigen Type Region* Adjuvant Immunization Route Model Route Dose ED50 Control Test Fisher's Exact Log-Rank
Koizumi et al., 2004 (14) His6 RPS-Ec LigA d1'-d13 (68-1224) Freund's SQ Mouse C3H/HeJ ip 106 <103 2/5 9/10 NS 0.025
LigB d1'-d12 (68-1191) 9/10 NS 0.036
Palaniappan et al., 2006 (12) GST RPS-Ec LigA d0'-d7' (32-630) + LigA d7'-d13 (631-1225) Al(OH)3 SQ Hamster ip 108 108 7/8 8/8 NS NA
4/5 5/5 NS NA
4/7 8/8 NS NA
Silva et al., 2007 (104) His6 RPF-Ec LigA d7'-d13 (625-1224) Freund's SQ Hamster ip 103 45 0/10 8/10 <0.001 <0.0001
LigB d2-d7' (131-645) 0/10 NS NS
LigB d7'-d12 (625-1259) 1/10 NS NS
Faisal et al., 2008 (105) DNA LigA d0'-d7' (32-630) + LigA d7'-d13 (631-1225) none IM Hamster ip 108 108 4/8 8/8 NS NA
5/8 8/8 NS NA
6/8 8/8 NS NA
Faisal et al., 2009 (106) RPS-Ec LigA d7'-d13 (631-1225) Al(OH)3 Hamster ip 108 108 0/8 4/8 NS <0.01
liposome SQ 0/8 7/8 <0.01 <0.001
PLGA 0/8 6/8 <0.01 0.001
Yan et al., 2009 (107) RPS-Ec + His6 RPS-Ec + RPS-Ec LigB d0'-d7' (32-630) + LigB d7'-d12 (631-1418) + LigB CTE (1419-1890) Al(OH)3 SQ Hamster ip 2×108 108 1/8 7/8 0.01 0.001
RPS-Ec LigB d0'-d7' (32-630) 6/8 <0.05 <0.01
His6 RPS-Ec Lig B d7'-d12 (631-1418) 4/8 NS NS
RPS-Ec LigB CTE (1419-1890) 3/8 NS NS
Cao et al., 2011 (108) RPS-Ec LigB d0'-d7' (32-630) Emulsigen SQ Hamster ip 250 100 0/6 2/6 NS <0.05
LigB d4 / LigB d12 3/6 NS <0.02
LigB d4-d7' / LigB d12 3/6 NS <0.05
Coutinho et al., 2011 (109) His6 RPS-Ec LigA d7'-d13 (631-1224) Freund's SQ Hamster ip 1000 50 0/4 4/4 <0.05 0.01
LigA d7'-d11 (631-1033) 2/4 NS 0.01
LigA d7'-d9 (631-851) 0/4 NS NS
LigA d10-d13 (852-1224) 4/4 <0.05 0.008
LigA d10-d12 (852-1124) 4/4 <0.05 0.008
LigA d11-d13 (943-1224) 4/4 <0.05 0.008
LigA d11-d12 (943-1124) 1/4 NS NS
LigA d12-d13 (1034-1224) 2/4 NS 0.01
Lucas et al., 2011 (110) His6-RPI-Ec LigA d7'-d13 (625-1224) Al(OH)3 NA Hamster ip 2000 10 2/10 0/10 NS NA
Forster et al., 2013 (111) DNA LigA d7'-d13 (629-1224) Al(OH)3 IM Hamster iph 10 2 0/6 0/8 NS NS
LigB: d7'-d12 (629-1112) 0/8 NS NS
LigB d0-d7' (1-628) 5/8 <0.05 <0.01
LigB CTE (1113-1501) 0/8 NS NS
LigB CTE (1502-1891) 0/8 NS NS
Lourdault et al., 2014 (112) Lipoprotein OspA SP / LigA d7'-d13 (631-1224) E. coli oral Hamster ip 1000 20 0/8 3/8 NS <0.0001
id 100 <10 0/8 5/8 <0.05 <0.02
Hartwig et al., 2014 (113) His6 mRP-Pp LigA d7'-d13 (625-1224) Al(OH)3 IM Hamster ip 1300 36 0/6 6/6 <0.01 <0.01
His6 dmRP-Pp LigA d7'-d13 (625-1224) 0/6 NS NS
Bacelo et al., 2014 (114) His6 RPF-Ec LigA d7'-d13 (625-1224) Al(OH)3 SQ Hamster ip 1300 36 0/6 4/6 NS <0.001
CpG 0/6 0/6 NS NS
xanthan 1/5 6/6 <0.05 <0.01
CpG + xanthan 6/6 <0.05 <0.01
Forster et al., 2015 (115) RPF-Ec p,b LigB d0-d7' (1-628) Al(OH)3 IM Hamster iph 10 2 0/5 0/6 NS <0.05
DNAp/RPF-Ecb 5/6 <0.02 <0.01
DNAp/DNAb 2/5 NS <0.01
DNAp/DNAb none 0/5 NS NS
Oliviera et al., 2016 (116) His6 RPF-Ec LigA d7'-d13 (625-1224) Al(OH)3 SQ Hamster ip 1300 260 0/6 4/6 NS <0.001
CpG 0/6 1/6 NS <0.01
CpG + MWCNT 0/6 1/6 NS <0.01
MWCNT 0/6 0/6 NS <0.01
Conrad et al., 2017 (117) His6 RPF-Ec LigB d2-d7' (131-645) Al(OH)3 IM Hamster ip 200 18 0/10 10/10 <0.0001 <0.0001
Evangelista et al., 2017 (118) His6 RPS-Ec LigA d7'-d13 (631-1224) Freund's SQ Hamster ip 105 20 0/5 8/8 <0.001 0.0001
LigB d0-d7 (19-672) 3/8 NS NS
LigA d7'-d11 (631-1224) + LigB d0-d7 (19-672) 8/8 <0.001 0.0001
Hsieh et al., 2017 (31) (NA) RPS-Ec LigB d7 (579-674) Al(OH)3 SQ Hamster ip 250 NA 1/6 0/6 NS NS
LigB d10 (848-943) 0/6 NS NS
LigB d10'(848-889) / d7'(621-674) 6/6 <0.02 <0.01
da Cunha et al., 2019 (119) His6 RPF-Ec p,b LigA d11-d13 (943-1224) / LigB d2-d7' (131-648) Al(OH)3 IM Hamster ip 200 40 0/8 8/8 <0.001 <0.001
His6 RPF-Ec p,b Montanide 8/8 <0.001 <0.001
DNAp/DNAb none/none 2/8 NS NS
DNAp/H6-RPFb none/
Al(OH)3
8/8 <0.001 <0.001
Techawiwattanaboon et al., 2019 (120) His6 RPF-Ec LigA d7'-13 (631-1224) liposome + MPL + QS21 SQ Hamster ip 200 20 0/5 3/5 NS <0.05
LigA d7'-d13 (631-1224) + LenA + LcpA + Lsa23 3/5 NS <0.01
Techawiwattanaboon et al., 2020 (121) His6 RPF-Ec LigA d7'-13 (631-1224) liposome + MPL + QS21 IM Hamster ip 200 20 0/5 3/5 NS <0.05
SQ 3/5 NS <0.05

Al(OH)3, aluminum hydroxide; GST, glutathione-S-transferase; RPS-Ec, recombinant protein produced in E. coli and purified as soluble protein; RPF-Ec, recombinant protein produced in E. coli, solubilized in urea, and folded; RPI-Ec, recombinant protein produced in E. coli and solubilized in urea; d, Ig-like domain; CTE, C-terminal extension; p, prime; b, boost; iph, intraperitoneal inoculation with a heterologous strain; SP, signal peptide; IM, intramuscular; SQ, subcutaneous; PLGA, poly-lactic-co-glycolic acid; mRP-Pp, mannosylated recombinant purified protein produced in Pichia pastoris; dmRP-Pp, demannosylated recombinant purified protein produced in Pichia pastoris, NS, not significant.

*Chimeric constructs are shown with sequences separated by a slash (/). LigA and LigB domains included in constructs are numbered. An apostrophe (‘) is used to indicate that the endpoint of the sequence lies within a domain. Amino acid coordinates are shown in parentheses.

** All experimental trials in a study may not be shown. In those cases, a representative trial is shown.