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Journal of General Virology (2000), 81, 1659-1667.
© 2000 Society for General Microbiology


Animal: RNA Viruses

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

Kanakatte Raviprakash1,2, Kevin R. Porter1, Tadeuscz J. Kochel1, Daniel Ewing1, Monica Simmons1, Irving Phillips1, Gerald S. Murphy1,2, Walter R. Weiss1 and Curtis G. Hayes1

Virology Program, Infectious Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Rm 3N71, Silver Spring, MD 20910-7500, USA1
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA2

Author for correspondence: Kanakatte Raviprakash. Fax +1 301 319 7451. e-mail ravik{at}nmripo.nmri.nnmc.navy.mil

A candidate DNA vaccine expressing dengue virus type 1 pre-membrane and envelope 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 time. Four of the eight i.m.-inoculated monkeys were protected completely from developing viraemia when challenged 4 months after the last dose with homologous 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 monkeys showed an anamnestic antibody response, indicating that they had established immunological memory. Vaccine-induced antibody had an avidity index similar to that of antibody induced by virus infection; however, no clear correlation was apparent between antibody avidity and virus neutralization titres.




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