TABLE 3.

Replication and immunogenicity in rhesus monkeys following a single dose of T-wt or TV-1, -2, or -3

Tetravalent formulation (n)aVirus replication determined by plaque assay in Vero cellsRelative level of replication of each component of tetravalent formulationbGeometric mean serum neutralizing antibody titer on day 28 (% seroconversion)d
Mean no. of viremic days/monkeyMean peak virus titer (log10 PFU/ml of serum)Total no. of virus clones analyzed (days)c% of each serotype among virus isolates (% of monkeys with at least one clone of indicated virus)
DEN1DEN2DEN3DEN4DEN1DEN2DEN3DEN4
T-wt (4)5.82.0 ± 0.2155 (1-8)69 (100)12 (100)8 (75)11 (100)289 (100)113 (100)243 (100)241 (100)
TV-1 (6)1.51.2 ± 0.144 (1-4)5 (33)5 (33)56 (83)34 (50)52 (100)67 (100)273 (100)79 (100)
TV-2 (16)1.31.3 ± 0.1125 (1-3)9 (50)7 (50)19 (56)65 (94)57 (81)16 (13)18 (19)126 (100)
TV-3 (6)1.51.4 ± 0.1214 (1-4)12 (100)9 (100)11 (83)68 (100)59 (100)117 (100)91 (100)144 (100)
  • a Groups of rhesus monkeys were inoculated subcutaneously with each formulation in a 1-ml dose. Serum was collected for days 0 to 6, 8, and 28. n = number of monkeys per group.

  • b Virus clones were isolated in Vero cells by terminal dilution of serum shown by plaque assay to contain virus. RNA was isolated from each virus clone and reverse transcribed, and the serotype was determined in a qPCR assay with serotype-specific primers as described in Materials and Methods.

  • c Virus clones were isolated from daily serum samples from days on which virus was detectable by plaque assay.

  • d Plaque reduction (60%) neutralizing antibody titers (reciprocal dilution) were determined using DEN1 Western Pacific, DEN2 New Guinea C prototype, DEN3-Sleman/78, and DEN4 Dominica/81. Percent seroconversion was defined as the percentage of monkeys with a fourfold or greater increase in neutralizing antibody titer after immunization.