Dengue virus type 1 DNA vaccine induces protective immune responses in rhesus macaques

A candidate DNA vaccine expressing dengue virus type 1 pre-membrane and env elope proteins was used to immunize rhesus macaques. Monkeys were immunized intramuscularly (i.m.) or intradermally (i.d.) by three or four 1 mg doses of vaccine, respectively. Monkeys that were inoculated i.m. seroconverted more quickly and had higher antibody levels than those that were inoculated i.d. The sera exhibited virus-neutralizing activity, which declined over t ime. Four of the eight i.m.-inoculated monkeys were protected completely fr om developing viraemia when challenged 4 months after the last dose with ho mologous dengue virus. The other four monkeys had reduced viraemia compared with the control immunized monkeys. The i.d.-inoculated monkeys showed no reduction in viraemia when challenged with the virus. All vaccinated monkey s showed an anamnestic antibody response, indicating that they had establis hed immunological memory. Vaccine-induced antibody had an avidity index sim ilar to that of antibody induced by virus infection; however, no clear corr elation was apparent between antibody avidity and virus neutralization titr es.