Virulence and immunogenicity of a temperature-sensitive dengue-2 virus in lower primates

Clones of dengue-2 virus were tested for virulence by inoculation of rhesus monkeys and chimpanzees. Although primates showed no overt signs of illness, inoculation with the parent virus or a subline of a large-plaque clone resulted in a viremia lasting 1 to 7 days. By these criteria, sublines of a small-plaque clone were significantly less virulent and produced little or no viremia in primate hosts. Although they had a substantially reduced viremia, primates inoculated with the small-plaque sublines showed stimulation of complement-fixing, hemagglutination-inhibiting, and neutralizing antibodies. The protection afforded rhesus monkeys 3 months after inoculation with two of the small-plaque sublines was demonstrated by a lack of viremia and a failure to escalate preexisting antibody levels after challenge with the parent virus. Both the S-1 subline and the parent virus had a limited capacity to produce central nervous system pathology in monkeys inoculated intrathalamically and intrathecally. Evidence thus far accumulated for primates indicates that the S-1 subline of dengue-2 virus has potential value as a candidate vaccine virus.