TABLE 2.
The set of five cp mutations attenuates RSV for the upper and lower respiratory tracts of chimpanzees
| Virus used to infect animala | Marker
|
Chimpanzee no.b | Mean virus titer (log10 PFU/ml)
|
Rhinorrhea scored
|
Days with cough | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nasal wash sample
|
Tracheal lavage sample
|
|||||||||||
| 4C | Site | HEK | cp | Peak titer | Daily titerc | Peak titer | Daily titerc | Peak | Mean | |||
| rD46 | X | 1 | 4.9 | 3.7 | 3.4 | 3.2 | 3 | 1.1 | 4 | |||
| X | 2 | 5.1 | 3.1 | 4.6 | 4.5 | 4 | 2.0 | 4 | ||||
| X | 3 | 4.4 | 3.9 | 4.0 | 2.5 | 3 | 1.4 | 5 | ||||
| X | 4 | 4.6 | 3.5 | 4.7 | 3.0 | 4 | 2.6 | 5 | ||||
| Mean ± SE | 4.8 ± 0.16 | 3.6 ± 0.15 | 4.2 ± 0.30 | 3.1 ± 0.33 | 3.5 | 1.8 | 4.0 | |||||
| A2 wte | X | 5* | 4.6 | 3.6 | 5.1 | 3.7 | 3 | 1.0 | 2 | |||
| X | 6* | 5.3 | 3.6 | 5.9 | 4.0 | 3 | 2.1 | 0 | ||||
| Mean ± SE | 5.0 ± 0.35 | 3.6 ± 0.30 | 5.5 ± 0.40 | 3.8 ± 0.46 | 3.0 | 1.6 | 1.0 | |||||
| rA2sites | X | X | 7 | 4.8 | 4.2 | 4.1 | 3.7 | 2 | 0.9 | 1 | ||
| X | X | 8 | 5.4 | 3.8 | 5.5 | 4.1 | 3 | 1.4 | 3 | |||
| X | X | 9 | 4.8 | 4.4 | 5.3 | 4.2 | 2 | 0.9 | 3 | |||
| X | X | 10 | 4.9 | 3.7 | 3.8 | 2.9 | 3 | 2.0 | 3 | |||
| Mean ± SE | 5.0 ± 0.14 | 4.0 ± 0.18 | 4.7 ± 0.43 | 3.7 ± 0.33 | 2.5 | 1.3 | 2.5 | |||||
| rA2cp | X | X | X | X | 11 | 4.3 | 2.1 | 4.5 | 3.3 | 2 | 1.1 | 0 |
| X | X | X | X | 12 | 3.8 | 2.7 | 1.0 | 1.0 | 2 | 0.9 | 0 | |
| X | X | X | X | 13 | 4.6 | 3.2 | 3.7 | 3.2 | 0 | 0 | 0 | |
| X | X | X | X | 14 | 4.8 | 3.5 | 3.8 | 2.4 | 0 | 0 | 0 | |
| Mean ± SE | 4.4 ± 0.22 | 2.9 ± 0.23 | 3.3 ± 0.77 | 2.7 ± 0.40 | 1.0 | 0.5 | 0.0 | |||||
| cpRSVf | X | X | 15* | 5.0 | 3.6 | 2.8 | 2.8 | 1 | 0.5 | 0 | ||
| X | X | 16* | 4.3 | 3.4 | 3.0 | 3.0 | 1 | 0.6 | 0 | |||
| Mean ± SE | 4.7 ± 0.35 | 3.5 ± 0.22 | 2.9 ± 0.10 | 2.9 ± 0.10 | 1.0 | 0.6 | 0.0 | |||||
Chimpanzees were inoculated by the intranasal and intratracheal routes with 104 PFU of the indicated virus in a 1-ml dose per site. Nasal wash samples were collected daily for 10 days, and tracheal lavage samples were collected on days 2, 5, 6, 8, and 10.
*, historic control animal from the work of Crowe et al. (7).
Mean daily titers were computed for each chimpanzee by adding together the virus titers from days with detectable levels of virus (≥0.7 PFU/ml) and dividing this sum by the total number of days with detectable virus titer.
The amount of rhinorrhea was estimated daily and assigned a score (0 to 4) that indicated extent and severity. Scores indicate severe (4), moderate (3), mild (2), trace (1), or no (0) rhinorrhea. Mean rhinorrhea scores represent the sum of scores during the 8 days of peak virus shedding divided by 8.
Biologically derived control virus (lot F-059) for which the presence of the HEK F-gene mutations was confirmed.
Biologically derived cp virus (lot 3131).