TABLE 3.
Only vaccinated mice survived the infection if 21 days of co-trimoxazole was initiated 93 h or 117 h post exposure to aerosolized B. pseudomallei.
| Vaccination status and treatment groupsa | % Survival through day 30 post challenge | Day 30 survival P-valueb |
% Survival through day 86 post challenge | Day 86 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 93 h | 0%f | NSd | 0% | NS | n/a | NS |
| PBS + co-trimoxazole 117 h | 0%g | NS | 0% | NS | n/a | 0.0018 |
| 668 ΔilvI | 30% | NS | 30% | NS | 3/3 | <0.0001 |
| 668 ΔilvI + co-trimoxazole 93 h | 100% | 0.0031 | 100% | 0.0031 | 9/10e | 0.0012 |
| 668 ΔilvI + co-trimoxazole 117 h | 100% | 0.0031 | 100% | 0.0031 | 9/10e | 0.0012 |
| AhpC + Hcp1 + conjugate | 80% | 0.0007 | 40% | NS | 4/4 | <0.0001 |
| AhpC + Hcp1 + conjugate + co-trimoxazole 93 h |
100% | NS | 100% | 0.0108 | 9/10e | 0.0039 |
| AhpC + Hcp1+ conjugate + co-trimoxazole 117 h |
100% | NS | 100% | 0.0108 | 9/10e | 0.0039 |
| Hcp1 + conjugate | 80% | 0.0007 | 70% | 0.0031 | 5/7e | <0.0001 |
| Hcp1 + conjugate + co-trimoxazole 93 h | 100% | NS | 100% | NS | 7/10e | NS |
| Hcp1 + conjugate + co-trimoxazole 117 h | 90% | NS | 90% | NS | 9/9 | NS |
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 1.57 × 103 CFU (+/− 2.34 × 102 CFU) of aerosolized B. pseudomallei K96243 on day 35 post-last vaccination. Sham vaccinated mice were not rescued from lethal infection with the delayed initiation of co-trimoxazole therapy.
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.
f50% of mice succumbed or were euthanized prior to co-trimoxazole initiation.
g100% of mice succumbed or were euthanized prior to co-trimoxazole initiation.