Table 3.
F. tularensis subsp. tularensis SCHU S4 mutants: Protection against SCHU S4 respiratory challenge.
| Vaccine | Host straina | Vaccine route, dose (CFU) | Boost (route) | LVS control (route) | Interval (days)b | SCHU S4 challenge route, dose (CFU or LD50)c | % Survival post-challenge (MST, days)d | References | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Vaccine | LVS | Sham | ||||||||
| NUTRIENT METABOLIC MUTANTS | ||||||||||
| ΔpurMCD | BALB/c | i.n., 104 | No | Yes (i.n.) | 42 | i.n., 100 | 14 (11) | 100 (21) | 0 (5) | Pechous et al., 2008 |
| i.n., 104 | No | Yes (i.n.) | 42 | i.n., 2000 | 0 (6) | 0 (7) | 0 (5) | Pechous et al., 2008 | ||
| i.n., 104 | Yes (i.n.) | Yes (i.n./i.n.) | 21 | i.n., 100 | 71 (18) | 100 (21) | 0 (5) | Pechous et al., 2008 | ||
| i.n., 104 | Yes (i.n.) | Yes (i.n./i/n.) | 21 | i.n., 2000 | 0 (7) | 33 (11) | 0 (5) | Pechous et al., 2008 | ||
| i.d., 101−6 | No | No | 21 | i.n., 500 | 0 (6-8) | ND | 0 (6) | Pechous et al., 2008 | ||
| i.n., 101−6 | No | No | 21 | i.n., 500 | 0 (6-11) | ND | 0 (6) | Pechous et al., 2008 | ||
| ΔFTT1019c (guaA) | C57BL/6 | i.n., 7 × 105 | No | No | 28 | i.n., 100 | 0 (4) | ND | 0 (4) | Santiago et al., 2015 |
| ΔFTT1317c (guaB) | C57BL/6 | i.n., 1 × 109 | No | No | 28 | i.n., 95 | 0 (6) | ND | 0 (4) | Santiago et al., 2015 |
| i.n., 6 × 107 | Yes (i.n.) | No | 28 | i.n., 100 | 0 (4) | ND | 0 (4) | Santiago et al., 2015 | ||
| ΔFTT1019c, ΔFTT1317c (guaA, guaB) | C57BL/6 | i.n., 1 × 108 | Yes (i.n.) | No | 28 | i.n., 100 | 0 (4) | ND | 0 (4) | Santiago et al., 2015 |
| ΔguaBA | Rabbits | i.d., 109 | No | Yes (i.d.) | 30 | Aero., 40 LD50 | 27 (7)* | 0 (7) | 0 (5) | Reed et al., 2014 |
| ΔaroD | Rabbits | i.d., 109 | No | Yes (i.d.) | 30 | Aero., 40 LD50 | 36 (7)* | 0 (7) | 0 (5) | Reed et al., 2014 |
| HEAT SHOCK PROTEIN MUTANTS | ||||||||||
| ΔclpB | BALB/c | i.d., 105 | No | Yes (i.d.) | 42 | Aero., 20 | 60 (28) | 0 (8) | 0 (5) | Conlan et al., 2010 |
| BALB/c | i.d., 105 | Yes (p.o.) | Yes (i.d./p.o) | 42 | Aero., 20 | 20 (11) | 0 (8) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | i.d., 105 | No | Yes (i.d.) | 42 | Aero., 20 | 0 (10) | 0 (11) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | i.d., 105 | Yes (p.o.) | Yes (i.d./p.o) | 42 | Aero., 20 | 0 (16) | 0 (7) | 0 (6) | Conlan et al., 2010 | |
| BALB/c | p.o., 108 | No | Yes (p.o.) | 42 | Aero., 20 | 40 (16) | 0 (5) | 0 (5) | Conlan et al., 2010 | |
| BALB/c | p.o., 108 | Yes (p.o.) | Yes (p.o./p.o) | 42 | Aero., 20 | 20 (11) | 0 (7) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | p.o., 108 | No | Yes (p.o.) | 42 | Aero., 20 | 0 (12) | 0 (5) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | p.o., 108 | Yes (p.o.) | Yes (p.o./p.o) | 42 | Aero., 20 | 60 (28) | 0 (7) | 0 (5) | Conlan et al., 2010 | |
| BALB/c | i.d., 105 | No | Yes (i.d.) | 42 | i.n., 10 | 100 | 30 | 0 (~5) | Shen et al., 2010 | |
| BALB/c | i.d., 105 | No | Yes (i.d.) | 42 | i.n., 100 | 80 | 0 | 0 (~5) | Shen et al., 2010 | |
| BALB/c | i.d., 105 | No | Yes (i.d.) | 42 | i.n., 1000 | 20 | 0 | 0 (~5) | Shen et al., 2010 | |
| BALB/c | i.d., 105 | No | No | 42 | i.n., 100 | ~75 | ND | 0 (~5) | Twine et al., 2012 | |
| C57BL/6 | i.d., 105 | No | No | 42 | i.n., 100 | 0 | ND | 0 (5) | Twine et al., 2012 | |
| BALB/c | i.d., 103 | No | No | 42 | i.n., 105 | ~100 | ND | 0 (5) | Golovliov et al., 2013 | |
| BALB/c | i.d., 105 | No | No | 42 | i.n., 105 | ~80 | ND | 0 (5) | Golovliov et al., 2013 | |
| BALB/c | i.d., 107 | No | No | 42 | i.n., 105 | ~60 | ND | 0 (5) | Golovliov et al., 2013 | |
| BALB/c | i.d., 105 | No | No | 42 | i.n., 40 | 100 | ND | 0 (~5) | Golovliov et al., 2013 | |
| ΔclpBΔcapB | BALB/c | i.d., 107 | No | Yes (i.d.) | 42 | Aero., 100 | ≤ 20 | 0 | ND | Golovliov et al., 2013 |
| CAPSULAR MUTANT | ||||||||||
| ΔFTT0918 ΔcapB |
BALB/c | i.d., 103 | No | Yes (i.d.) | 42 | Aero., 2 | 40 (8) | 0 (8) | 0 (5) | Conlan et al., 2010 |
| i.d., 103 | Yes (p.o.) | Yes (i.d./p.o) | 42 | Aero., 2 | 0 (8) | 0 (8) | 0 (5) | Conlan et al., 2010 | ||
| p.o., 108 | No | Yes (p.o.) | 42 | Aero., 2 | 0 (5) | 0 (5) | 0 (5) | Conlan et al., 2010 | ||
| p.o., 108 | Yes (p.o.) | Yes (i.d./p.o.) | 42 | Aero., 2 | 0 (8) | 0 (7) | 0 (5) | Conlan et al., 2010 | ||
| C3H/HeN | i.d., 103 | No | Yes (i.d.) | 42 | Aero., 20 | 0 (5) | 0 (11) | 0 (5) | Conlan et al., 2010 | |
| i.d., 105 | Yes (p.o.) | Yes (i.d./p.o.) | 42 | Aero., 20 | 50 (17) | 0 (7) | 0 (6) | Conlan et al., 2010 | ||
| p.o., 108 | No | Yes (p.o.) | 42 | Aero., 20 | 0 (5) | 0 (5) | 0 (5) | Conlan et al., 2010 | ||
| p.o., 108 | Yes (p.o.) | Yes (p.o./p.o.) | 42 | Aero., 20 | 0 (5) | 0 (7) | 0 (6) | Conlan et al., 2010 | ||
| LIPOPROTEIN MUTANTS | ||||||||||
| ΔFTT1103 | C57BL/6 | i.n., 3 × 107 | No | No | 32 | i.n., 68 | 100 | ND | 0 (5) | Qin et al., 2009 |
| i.n., 1 × 108 | No | No | 32 | i.n., 37 | 100 | ND | 0 (5) | Qin et al., 2009 | ||
| i.n., 3 × 108 | No | No | 32 | i.n., 68 | 50 (18) | ND | 0 (5) | Qin et al., 2009 | ||
| BALB/c | i.n., 1 × 108 | No | No | 33 | i.n., 95 | 75 (21) | ND | 0 (5) | Qin et al., 2009 | |
| ΔFTT1103 (fipB) |
Rabbits | i.d., 109 | No | Yes (i.d.) | 30 | Aero., 40 LD50 | 0 (6) | 0 (7) | 0 (5) | Reed et al., 2014 |
| OTHER MUTANTS | ||||||||||
| ΔFTT0918 | BALB/c | i.d., 105 | No | Yes (i.d.) | 63 | Aero., 10* | 33 (15) | 0 (7) | 0 (5) | Twine et al., 2005 |
| ΔiglC | BALB/c | i.d., 107 | No | Yes (i.d.) | 63 | Aero., 10* | 0 (6) | 0 (7) | 0 (5) | Twine et al., 2005 |
| ΔiglC | BALB/c | i.d., 105 | No | Yes (i.d.) | 42 | Aero., 20 | 0 (6) | 0 (8) | 0 (5) | Conlan et al., 2010 |
| BALB/c | p.o., 108 | No | Yes (p.o.) | 42 | Aero., 20 | 0 (5) | 0 (5) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | i.d., 105 | No | Yes (i.d.) | 42 | Aero., 20 | 0 (5) | 0 (11) | 0 (5) | Conlan et al., 2010 | |
| C3H/HeN | p.o., 108 | No | Yes (p.o.) | 42 | Aero., 20 | 0 (5) | 0 (5) | 0 (5) | Conlan et al., 2010 | |
| ΔFTT0369c | BALB/c | i.d., 50 | No | No | 45 | i.n., 10 | 90 | ND | 0 (5) | Rockx-Brouwer et al., 2012 |
| i.n., 10 | No | No | 45 | i.n., 10 | 80 | ND | 0 (5) | Rockx-Brouwer et al., 2012 | ||
| ΔFTT1676 | BALB/c | i.d., 50 | No | No | 45 | i.n., 10 | 100 | ND | 0 (5) | Rockx-Brouwer et al., 2012 |
| i.n., 10 | No | No | 45 | i.n., 10 | ~50 | ND | 0 (5) | Rockx-Brouwer et al., 2012 | ||
| ΔFTT0369 ΔFTT1676 |
BALB/c | i.d., 50 | No | No | 45 | i.n., 10 | 60 | ND | 0 (5) | Rockx-Brouwer et al., 2012 |
| i.n., 10 | No | No | 45 | i.n., 10 | 10 | ND | 0 (5) | Rockx-Brouwer et al., 2012 | ||
a
Host strain: Mice: BALB/c, C57BL/6, or C3H/HeN mice; Rabbits: New Zealand White rabbits.
b
Interval: time between the only or the last vaccination and challenge.
c
SCHU S4 challenge route: *challenged with subsp. tularensis (Type A) FSC033 strain.
d
Survival: % survival after challenge of mice immunized with the vaccine candidate (vaccine), LVS control (LVS), or no vaccine or PBS control (Sham). MST, mean/median survival time;
*
Time to death does not include survivors; ND, not determined.