A dengue virus serotype-1 DNA vaccine induces virus neutralizing antibodies and provides protection from viral challenge in Aotus monkeys

A DNA vaccine that expresses the premembrane/membrane (prM) and envelope (E ) genes of dengue virus serotype-1 was tested for immunogenicity and protec tion against dengue-1 virus challenge in Aotus nancymae monkeys. The vaccin e, in 1 mg doses, was administered intradermally (ID) to three monkeys and intramuscularly (IM) to three others, For controls, a 1 mg dose of vector D NA was administered ID to two monkeys and IM to one. All animals were prime d and then boosted at one and five months post priming. Sera were collected monthly and analyzed for dengue-1 antibodies by enzyme linked immunosorben t assay (ELISA) and plaque reduction neutralization test (PRNT). Dengue-1 a ntibodies were detectable in the sera from ID and IM vaccine inoculated ani mals one month after the first boast and peaked one month after the second boost. The antibody levels from sera of animals that received the vaccine v ia the ID route were twice those from sera of animals that received the vac cine via the IM route. Six months after the second boost all inoculated and two naive monkeys were challenged with 1.25 x 10(4) plaque forming units ( PFU) of dengue-1 virus. Two vaccine immunized animals were protected from v iremia while the others showed a reduction in viremia. The mean days of vir emia were 1 and 1.3 for the animals that were immunized with the vaccine vi a the ID or IM route, respectively vs 4 and 2 mean days of viremia in the a nimals inoculated with control DNA. Naive animals were viremic for an avera ge of 4 days. All of the three control monkeys that received control DNA in oculum by either the ID or IM route had an intermittent viremia pattern wit h one or more negative days interspersed between the positive days. This pa ttern was not observed in any of the vaccine recipients or the naive contro l monkeys. These results demonstrate that DNA immunization is a promising a pproach for the development of dengue vaccines and that A. nancymae monkeys are suitable for dengue vaccine trials. (C) 2000 Elsevier Science Ltd. All rights reserved.