TABLE 2.
Vaccinated or naïve C57BL/6 mice are similarly protected after receiving 7 days of co-trimoxazole initiated within 45 h after exposure to aerosolized B. pseudomallei. Only vaccinated mice survived when co-trimoxazole was initiated 69 h post-exposure.
Vaccination status and treatment groupsa | % Survival through day 30 post challenge | Day 30 survival P-valueb |
% Survival through day 70 post challenge | Day 70 survival P-valueb |
Ratio of Sterile survivors/Total Survivorsc | TTM P-valueb |
PBS | 0% | n/a | 0% | n/a | n/a | n/a |
PBS + co-trimoxazole 9 h | 100% | <0.0001 | 100% | <0.0001 | 10/10 | <0.0001 |
PBS + co-trimoxazole 21 h | 100% | <0.0001 | 90% | 0.0001 | 6/9e | 0.0001 |
PBS + co-trimoxazole 45 h | 70% | 0.0031 | 70% | 0.0031 | 6/7e | 0.0002 |
PBS + co-trimoxazole 69 h | 0% | NSd | 0% | NS | n/a | NS |
668 ΔilvI | 20% | NS | 20% | NS | 1/2e | <0.0001 |
668 ΔilvI + co-trimoxazole 9 h | 100% | 0.0007 | 90% | 0.0055 | 10/10 | 0.0007 |
668 ΔilvI + co-trimoxazole 21 h | 100% | 0.0007 | 100% | 0.0007 | 10/10 | 0.0003 |
668 ΔilvI + co-trimoxazole 45 h | 100% | 0.0007 | 100% | 0.0007 | 7/10e | 0.0003 |
668 ΔilvI + co-trimoxazole 69 h | 90% | 0.0055 | 80% | 0.0230 | 6/8e | 0.0017 |
AhpC + Hcp1 + conjugatef | 56% | 0.0325 | 22% | NS | 2/2 | <0.0001 |
AhpC + Hcp1 + conjugate + co-trimoxazole 9 hf |
100% | 0.0294 | 100% | 0.0023 | 9/9 | 0.0008 |
AhpC + Hcp1 + conjugate + co-trimoxazole 21 hg | 100% | 0.0294 | 100% | 0.0023 | 8/8 | 0.0015 |
AhpC + Hcp1 + conjugate + co-trimoxazole 45 hf |
100% | 0.0294 | 100% | 0.0023 | 8/9e | 0.0008 |
AhpC + Hcp1 + conjugate + co-trimoxazole 69 hf |
100% | 0.0294 | 89% | 0.0152 | 8/9e | 0.0020 |
Hcp1 + conjugate | 60% | 0.0108 | 20% | NS | 2/2 | <0.0001 |
Hcp1 + conjugate + co-trimoxazole 9 hf |
100% | NS | 100% | 0.0007 | 9/9 | 0.0005 |
Hcp1 + conjugate + co-trimoxazole 21 h |
90% | NS | 90% | 0.0055 | 9/9 | 0.0031 |
Hcp1 + conjugate + co-trimoxazole 45 h |
100% | NS | 100% | 0.0007 | 9/10e | 0.0003 |
Hcp1 + conjugate + co-trimoxazole 69 hf |
100% | NS | 100% | 0.0007 | 8/9e | 0.0005 |
Only vaccinated mice survived the infection when co-trimoxazole was initiated at 69 h post exposure.
aMice were vaccinated as described in Section “Materials and methods.” If co-trimoxazole was provided it was initiated at the time-point after exposure to approximately 2.45 × 103 CFU (+/− 4.33 × 102 CFU) of aerosolized B. pseudomallei K96243 on day 35 post-last vaccination.
bStatistical comparison to respective control group without co-trimoxazole or in the case of vaccines only to the PBS alone group. P-values indicate the result of a Log-rank or Fisher exact test for the survival and TTM, respectively.
cSurvivors were determined to be free of B. pseudomallei CFU in lungs and spleens and there was no visible pyogranuloma formation noted at gross necropsy.
dNS, not significant.
eSee Supplementary Table 2 for bacterial burden data for each mouse shown to retain B. pseudomallei. Limit of detection for tissue homogenates is 5 CFU/organ.
fN = 9.
gN = 8.