Table 1a.
Evaluation of TB activity induced by active immunization in DFA: Mice were immunized with Pvs25-derived immunogens (or controls) as shown in Fig. 2. Each regime contained 10 immunized mice and was sub-divided into two groups, each containing five mice. Each group was then challenged with P. berghei Pvs25DR3 (5 mice) or WT P. berghei 2.34 (five mice), and used to assess transmission to mosquitoes via DFA. Each mouse was injected with 106 parasites. Mosquito midguts were dissected 10–12 days post feed. Mean intensities and prevalence were calculated from all mice. (a) For both regimes 2 and 4 with WT P. berghei challenge, mice developed cerebral malaria and were humanely culled before DFA could be performed, resulting in only four mice per group. Overall transmission blockade (in terms of both infection intensity and prevalence) was calculated by comparison to mice in the relevant immunized control groups. (b) Significance was assessed using Mann–Whitney U-test (to examine the difference in mean oocyst intensity) and the Fisher's exact probability test (to examine the difference in infection prevalence) (p < 0.05). Following challenge with WT P. berghei 2.34, no significant changes in either intensity or prevalence were observed with any immunization regime. Significant inhibition was only observed following challenge with Pvs25DR3. a = p < 0.05, Mann–Whitney U-test; b = p < 0.05, Fisher's exact probability test. Table 1 Evaluation of transmission-blocking activity by active immunization and DFA (a). Transmission following immunization, parasite challenge and DFA.
| Challenge | Total mosquitoes | Mean infection intensity (±SEM) | Mean infection prevalence | |
|---|---|---|---|---|
| Regime 1: Pvs25-FhCMB Abisco-100 | Pb Pvs25DR3 challenge (n = 5) | n = 248 | 0.48 (0.18) | 18.6% |
| Pb 2.34 challenge (n = 5) | n = 171 | 40.8 (5.10) | 96.8% | |
| Regime 2: Pvs25-FhCMB Alhydrogel | Pb Pvs25DR3 challenge (n = 5) | n = 199 | 0.66 (0.29) | 19.6% |
| Pb 2.34 challenge (n = 4) | n = 135 | 40.7 (5.90) | 95.3% | |
| Regime 3: Pvs25-ChAd63 - MVA | Pb Pvs25DR3 challenge (n = 5) | n = 226 | 0.99 (0.39) | 25.8% |
| Pb 2.34 challenge (n = 4) | n = 148 | 45.1 (6.10) | 93.6% | |
| Regime 4: Pvs25-ChAd63 - Pvs25-FhCMB -Abisco-100 | Pb Pvs25DR3 challenge (n = 5) | n = 250 | 0.39 (0.17) | 13.2% |
| Pb 2.34 challenge (n = 5) | n = 142 | 42.8 (5.73) | 98.0% | |
| Regime 5: LicKM-Abisco-100 | Pb Pvs25DR3 challenge (n = 5) | n = 255 | 1.37 (0.40) | 40.4% |
| Pb 2.34 challenge (n = 5) | n = 129 | 43.7 (8.66) | 90.8% | |
| Regime 6: LicKM-Alhydrogel | Pb Pvs25DR3 challenge (n = 5) | n = 239 | 1.51 (0.47) | 39.7% |
| Pb 2.34 challenge (n = 5) | n = 175 | 40.2 (5.80) | 88.6% | |
| Regime 7: GFP-ChAd63 - MVA | Pb Pvs25DR3 challenge (n = 5) | n = 227 | 1.59 (0.54) | 40.1% |
| Pb 2.34 challenge (n = 5) | n = 167 | 38.0 (5.14) | 94.0% | |
| Regime 8: GFP-ChAd63–LicKM-Abisco-100 | Pb Pvs25DR3 challenge (n = 5) | n = 214 | 1.54 (0.51) | 41.7% |
| Pb 2.34 challenge (n = 5) | n = 134 | 41.8 (6.1) | 93.3% |