Table 5.
Attenuation and protective efficacy against SCHU S4 respiratory challenge of F. tularensis vaccine candidates relative to LVS.
| Vaccinea | LD50 in mice (route, strain) | Efficacy ≥ LVS in mice against respiratory challenge with SCHU S4 (host strain)b | Vaccination—challenge interval (days) and other comments | References | ||
|---|---|---|---|---|---|---|
| i.d. | i.n. | p.o. | ||||
| LVS | ~103 (i.n. BALB/c) >107 (i.d. BALB/c) >108 (p.o., C3H/HeN) |
Toxicity | Fortier et al., 1991; Jia et al., 2009; Conlan et al., 2010 | |||
| MORE ATTENUATED THAN LVS | ||||||
| LVS ΔpurMCD | >106 (i.n. BALB/c) | Yes with boost (BALB/c) | 21 | Pechous et al., 2008 | ||
| LVS sodBFt | >104 (i.n. C57BL/6) >104 (i.n. BALB/c) | Yes (C57BL/6) | 21 | Bakshi et al., 2006, 2008 | ||
| FSC200 ΔclpB | >105 (i.n. BALB/c) | Yes (BALB/c) | 42; Less attenuated than LVS in SCID mice | Golovliov et al., 2013 | ||
| LVS ΔcapB | >107 (i.n. BALB/c) >108 (i.d. BALB/c) | No (BALB/c) | Yes (BALB/c) | 42; Need i.n. vaccination | Jia et al., 2010, 2013, 2016 | |
| LVS ΔcapB /IglA |
Yes (BALB/c) | 42 | Jia et al., 2013 | |||
| LVS ΔcapB /IglC |
Yes (BALB/c) | 42 | Jia et al., 2013 | |||
| LVS ΔcapB /IglABC |
Yes (BALB/c) | Yes (BALB/c) | 42 | Jia et al., 2016, 2018 | ||
| LVS::wzy | >107 (i.n. BALB/c) | Yes (BALB/c) | 28 | Kim et al., 2012 | ||
| LVS::wbtA | >107 (i.n. BALB/c) | No (BALB/c) | 28 | Sebastian et al., 2007; Kim et al., 2012 | ||
| Fn ΔiglD | >9.7 × 108 (i.n. BALB/c) | 30; No protection in BALB/c mice; relevant efficacy to LVS in mice and rats not known; efficacy in NHP equivalent to LVS | Chu et al., 2014 | |||
| SCHU S4 ΔpurMCD |
>106 (i.d. BALB/c) >106 (i.n. BALB/c) | Yes with boost (BALB/c) | 21; Single deletion | Pechous et al., 2008 | ||
| SchuS4 ΔgurBA |
>108 (in. C57BL/6) | 30; Efficacious in rabbits; single deletion | Reed et al., 2014; Santiago et al., 2015 | |||
| SCHU S4 ΔfipB |
>1010 (i.n. C57BL/6) | 30; Less efficacious than LVS in rabbits; single deletion | Qin et al., 2009 Reed et al., 2014 | |||
| SCHU S4 ΔiglC |
>108 (i.d. BALB/c) | 42 or 63; Not efficacious; single deletion | Twine et al., 2005; Conlan et al., 2010 | |||
| LVS ΔcapB + rLm/iglC |
>107 (i.d. BALB/c) for both vaccines | Yes (BALB/c) | 42 | Jia et al., 2009, 2013 | ||
| LVS ΔcapB/IglC + rLm/iglC |
>107 (i.d. BALB/c) for both vaccines | Yes (BALB/c) | 42 | Jia et al., 2009, 2013 | ||
| VIRULENCE EQUIVALENT TO LVS | ||||||
| SCHU S4 ΔclpB |
>107 (i.d. BALB/c) | Yes (BALB/c) | Yes (BALB/c) | 42; Single deletion | Conlan et al., 2010; Shen et al., 2010 | |
| SCHU S4 ΔclpBΔcapB |
>107 (i.d. BALB/c) | Yes (BALB/c) | 42; Survival ≤ 20% | Golovliov et al., 2013 | ||
| LESS ATTENUATED THAN LVS | ||||||
| SCHU S4 ΔFTT0918 |
~105 (i.d. BALB/c) | Yes (BALB/c) | 42; More virulent than LVS in mice | Twine et al., 2005 | ||
| SCHU S4 ΔFTT0918 ΔcapB |
≥ 107 (i.d. BALB/c) ~103 (i.d. C3H/HeN) | Yes (BALB/c) | Yes (C3H/HeN) | 42; Protection in C3H mice ≥ LVS with i.d. prime and oral boost; more virulent than LVS in C3H mice | Conlan et al., 2010 | |
| VIRULENCE NOT COMPARED WITH LVS | ||||||
| SchuS4 ΔaroD |
Not available | 21; More protective than LVS in rabbits; single deletion | Reed et al., 2014 | |||
a
Vaccine: Only vaccines that were tested against subsp. tularensis (Type A) respiratory challenge and compared with LVS are listed.
b
Efficacy relative to LVS: Percentage survival was used to compare the protective efficacy against respiratory challenge with a subsp. tularensis Type A strain between animals immunized with the vaccine candidate and animals immunized with LVS. Statistical significance was not available from some of the reported studies.