TABLE 1.
Neurovirulence of ChimeriVax-DEN1-4 viruses at various Vero passages in 4-day-old mice
| Virus chimera | Expt | Passagea | Amino acid changesb | Dose (BT)c | Mortality (no. of dead/total no.) | LD50 (log10 PFU) |
|---|---|---|---|---|---|---|
| DEN1 | 1 | P7 (PMS) | None | 3.1, 2.1 | 10/11, 8/11 | <2.1 |
| P8 (GMP MS) | E204K→R | 2.6, 1.6 | 7/11, 8/11 | <1.6 | ||
| P9 | NDd | 4.1, 3.1 | 2/11, 3/11 | >4.1 | ||
| P10 | E204K→R | 5.1, 4.1, 3.1 | 1/13, 1/13, 0/12 | >5.1 | ||
| 2 | P7 | None | 2.9, 1.9 | 10/10, 8/10 | <1.9 | |
| P20 | E204K→R, NS4b23 (S→I), NS4b98(V→I) | 3.8, 2.8 | 0/9, 0/9 | >3.8 | ||
| DEN2 | 1 | P7 (PMS) | None | 3.3, 2.3 | 11/11, 8/11 | <2.3 |
| P8 (GMP MS) | prM24L→V, E251V→F | 2.0, 1.0 | 11/11, 9/11 | <1.0 | ||
| P9 | ND | 3.8, 2.8 | 11/12, 10/12 | <2.8 | ||
| P10 | prM24L→V, E251V→F | 4.0, 3.0, 2.0 | 11/12, 10/13, 5/13 | 2.7 | ||
| 2 | P7 (PMS) | None | 3.3, 2.3, 1.3 | 10/10, 8/10, 6/10 | 1.3 | |
| P20 | prM24L→V, E251V→F | 3.6, 2.6, 1.6 | 7/9, 4/10, 2/9 | 3.5 | ||
| DEN3 | 1 | P7 (PMS) | None | 3.6 | 4/12 | >3.6 |
| P8 (GMP MS) | None | 3.5 | 3/12 | >3.5 | ||
| P9 | ND | 4.0, 3.0 | 0/13, 0/13 | >4.0 | ||
| P10 | E202K→R | 3.7, 2.7 | 0/13, 0/13 | >3.7 | ||
| 2 | P7 (PMS) | None | 4.6, 3.6 | 2/10, 2/10 | >4.6 | |
| P20 | NS4b177L→F | 4.1, 3.1 | 0/10, 0/10 | >4.1 | ||
| DEN4 | 1 | P7 (PMS) | None | 2.3, 1.3 | 9/11, 6/11 | 2.2 |
| P8 (GMP MS) | None | 2.5, 1.5 | 11/12, 9/11 | <1.5 | ||
| P9 | ND | 2.4, 1.4 | 8/11, 1/12 | 1.9 | ||
| P10 | None | 4.0, 3.0, 2.0 | 12/13, 7/13, 4/13 | 2.4 | ||
| 2 | P7 (PMS) | None | 2.6, 1.6, 0.6 | 4/11, 3/11, 0/11 | >2.6 | |
| P20 | None | 3.7, 2.7, 1.7 | 2/11, 1/11, 0/11 | >3.7 | ||
| YF-VAX | 1 | None | NAd | 2.2 | 15/15 | <2.2 |
| 2 | None | NA | 2.2 | 9/9 | <2.2 |
a
P9 and P10 viruses were produced in the research laboratory by two passages of GMP MS (P8) in Vero cells.
b
No silent mutation was found in any viruses except for DEN3 virus (a nucleotide change in NS4A6607 was found in all passages of DEN3 virus chimeras).
c
Doses were determined by back titer determination (BT) of inocula.
d
ND, not done; NA, not applicable.