Table 3.
Level of replication of HPIV1 vaccine candidates in the upper and lower respiratory tract of African green monkeys.
| Mean peak virus titer (log10 TCID50/ml)c | Mean sum of the daily virus titers (log10 TCID50/ml)d | atte | |||||||
| Virusa | Shut-off temperature b | No. of animals | NP swabf | TL g | NP swabf | TL g | URT | LRT | |
| 1 | HPIV1 wt | - | 14 | 4.2 ± 0.2 | 3.9 ± 0.3 | 26.4 ± 1.5 | 12.2 ± 1.6 | - | - |
| 2h | rHPIV1-CR84G | - | 4 | 3.6 ± 0.4 | 4.0 ± 0.5 | 21.0 ± 1.7 | 11.7 ± 2.5 | No | No |
| 3h | rHPIV1-CR84GHNT553A | - | 12 | 2.1 ± 0.2i | 4.8 ± 0.3 | 10.5 ± 0.9 | 14.3 ± 1.1 | Yes | No |
| 4h | rHPIV1-CΔ170 | - | 6 | 3.4 ± 0.5 | 2.3 ± 0.5 | 14.8 ± 1.9 | 5.1 ± 0.8 | Yes | Yes |
| 5 | rHPIV1-LY942A | 37°C | 4 | 2.3 ± 0.1 | 2.3 ± 0.2 | 16.9 ± 0.7 | 8.4 ± 1.2 | Yes | Yes |
| 6h | rHPIV1-CR84GHNT553ALY942A | 37°C | 8 | 2.4 ± 0.2 | 2.1 ± 0.3 | 12.9 ± 1.0 | 5.1 ± 0.6 | Yes | Yes |
| 7 | rHPIV1-CR84GLΔ1710–11 | 36°C | 4 | 1.5 ± 0.4 | 0.9 ± 0.2 | 8.6 ± 1.8 | 3.2 ± 0.6 | Yes | Yes |
| 8 | rHPIV1-CR84G/Δ170HNT553ALY942A | 38°C | 4 | 1.2 ± 0.3 | 0.6 ± 0.1 | 5.9 ± 0.5 | 2.6 ± 0.1 | Yes | Yes |
| 9 | rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 | 35°C | 4 | 0.9 ± 0.3 | ≤0.5 ± 0.0 | 6.3 ± 0.5 | ≤2.5 ± 0.0 | Yes | Yes |
a Monkeys were inoculated i.n. and i.t. with 106 TCID50 of the indicated virus in a 1 ml inoculum at each site. Data are representative of one to five experiments.
b Shut-off temperature is defined in footnote d, Table 2.
c Virus titrations were performed on LLC-MK2 cells at 32°C and expressed as the mean ± S.E of the individual peak virus titers for the animals in each group irrespective of day. The limit of detection was 0.5 log10 TCID50/ml.
d Mean sum of the daily virus titers: the sum of the titers for all of the days of sampling was determined for each animal individually, and the mean was calculated for each group. On days when virus was not detected, a value of was 0.5 log10 TCID50/ml was assigned for the purpose of calculation. The mean sum of the lower limit of detection was 5.0 log10 TCID50/ml for NP swabs and 2.5 log10 TCID50/ml for TL samples.
e Virus is designated att in the URT or LRT based on a significant reduction in either mean peak titer or mean sum of daily titers compared to the HPIV1 wt group (see footnote h).
f Nasopharyngeal (NP) swab samples were collected on days 1–10 post-infection.
g Tracheal lavage (TL) samples were collected on days 2, 4, 6, 8, and 10 post-infection.
h These data have been previously published [13] [15] [16] and are included here for the purposes of comparison.
i Underlined values indicate a statistically significant reduction compared to corresponding HPIV1 wt titer, P < 0.05 (Student-Newman-Keuls multiple comparison test).