title: Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys.
abstract: The feasibility of a purified, inactivated dengue (DEN) vaccine made in Vero cells was explored. A DEN-2 virus candidate was chosen for production of a monotypic, purified, inactivated vaccine (PIV). Virus was harvested from roller bottle culture supernatants, concentrated, and purified on sucrose gradients. The purified virus was inactivated with 0.05% formalin at 22 degrees C. After inactivation, the virus retained its antigenicity and was immunogenic in mice and rhesus monkeys, in which it elicited high titers of DEN-2 virus-neutralizing antibody. Mice were completely protected against challenge with live, virulent virus after receiving two 0.15-microg doses of PIV. Monkeys vaccinated with three doses ranging as low as 0.25 microg demonstrated complete absence or a significant reduction in the number of days of viremia after challenge with homologous virus. These results warrant further testing and development of PIVs for other DEN virus serotypes.
authors.affiliation: Walter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, Washington, DC 20307-5100, USA.
authors.forename: R
authors.initials: R
authors.lastname: Putnak
authors.forename: D A
authors.initials: DA
authors.lastname: Barvir
authors.forename: J M
authors.initials: JM
authors.lastname: Burrous
authors.forename: D R
authors.initials: DR
authors.lastname: Dubois
authors.forename: V M
authors.initials: VM
authors.lastname: D'Andrea
authors.forename: C H
authors.initials: CH
authors.lastname: Hoke
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: K H
authors.initials: KH
authors.lastname: Eckels
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D015153:Blotting, Western; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient / Q000379:methods; D002522:Chlorocebus aethiops; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control*; D003716:Dengue Virus / Q000254:growth & development / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology; D006385:Hemagglutination Inhibition Tests; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D014709:Vero Cells; D014766:Viremia / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D005557:Formaldehyde