Article Figures & Data
Tables
- Table 1.
rA2ΔNS1 and rA2ΔM2-2 are highly attenuated in both the upper and lower respiratory tracts of chimpanzees but are highly immunogenic
Virus used to infect chimpanzeesa No. of animals Doseb (per site, log10PFU) Mean peak virus titerc(log10 PFU/ml) ± SE (Duncan grouping) Mean peak rhinorrhea scored (range, 0–4) Mean neutralizing antibody titer in serume (reciprocal log2) Nasopharyngeal swab Tracheal lavage Day 0 Day 28 Wild-type RSV A2f 2 4.0 5.0 ± 0.35 (A) 5.5 ± 0.40 (A) 3.0 <3.3 11.2 rA2g 2 4.0 4.9 ± 0.15 (A) 5.4 ± 0.05 (A) 2.5 <3.3 10.5 rA2ΔSHg 3 4.0 4.6 ± 0.10 (A) 3.8 ± 0.31 (B) 1.0 <3.3 10.2 rA2ΔNS2g 4 4.0 3.8 ± 0.41 (B) 1.4 ± 0.29 (C) 1.0 3.4 10.6 rA2cp248/404g 4 5.0 2.5 ± 0.25 (C) 1.4 ± 0.37 (C) 0.8 3.4 10.6 rA2ΔNS1 4 5.0 1.6 ± 0.12 (D) 1.2 ± 0.43 (C) 2.0 <3.3 9.8 rA2ΔM2-2 4 5.0 1.5 ± 0.09 (D) <0.7 1.8 <3.3 9.1 ↵a All recombinant-derived viruses contain the sites and HEK mutations (see the text), except for rA2ΔM2-2.
↵b Chimpanzees were inoculated by the intranasal and intratracheal routes with the indicated amount of virus in a 1-ml inoculum per site.
↵c Nasopharyngeal swab samples were collected daily for 10 days, and tracheal lavage samples were collected on days 2, 5, 6, 8, and 10. Mean peak titers were calculated and assigned to statistically similar groups by Duncan's multiple-range test (α = 0.05). Means in each column with different letters are significantly different.
↵d 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. Shown are the mean peak scores.
↵e Serum RSV-neutralizing antibody titers were determined by a complement-enhanced 60% plaque reduction assay using wild-type RSV A2 and HEp-2 cell monolayer cultures incubated at 37°C. RSV-seronegative chimpanzee serum used as a negative control had a neutralizing antibody titer of <3.3 log2 reciprocal. Adult human serum used as a positive control had a neutralizing antibody titer of 11.4 log2 reciprocal.
↵f Historic controls from the study of Crowe et al. (10).
↵g Data from the study of Whitehead et al. (29).
- Table 2.
Infection of chimpanzees with rA2ΔNS1 or rA2ΔM2-2 induced significant protection against subsequent challenge with wild-type RSV A2 in the upper and lower respiratory tracts
Immunizing virus Inoculum dosea (log10PFU/ml) No. of animals Replication of RSV challenge virus at the indicated siteb Mean peak rhinorrhea score Nasopharynx Trachea Mean no. of days of shedding ± SE Mean peak titerc ± SE Mean no. of days of shedding ± SE Mean peak titer ± SE rA2ΔNS1 5.0 4 2.8 ± 0.75 1.7 ± 0.46 1.0 ± 0.41 1.8 ± 0.73 1.0 rA2ΔM2-2 5.0 4 3.5 ± 0.87 2.3 ± 0.71 1.0 ± 0.71 1.7 ± 0.63 1.0 rA2ΔNS2d 4.0 4 ND 1.9 ± 0.30 ND 2.2 ± 0.77 1.0 cpts248/404e 4.7 2 3.5 ± 0.50 2.3 ± 0.25 0 <0.7 1.0 Nonee 2 8.5 ± 0.50 5.0 ± 0.35 6.0 ± 1.0 4.8 ± 0.30 3.0 ↵a Each virus was initially administered at the indicated dose in a 1.0-ml inoculum given intranasally and intratracheally.
↵b On day 56, chimpanzees were challenged with wild-type RSV A2 administered at a dose of 104 PFU/ml in a 1.0-ml inoculum given intranasally and intratracheally. Nasopharyngeal swab samples were collected daily for 12 days, and tracheal lavage samples were collected on days 2, 5, 6, 8, and 12. ND, not determined.
↵c Mean peak titers (log10 PFU/ml) were calculated by using the peak virus titer achieved in each animal.
↵d Data from the study of Whitehead et al. (29).
↵e Historic control animals from the study of Crowe et al. (10) were used.
