Development of a purified, inactivated, dengue-2 virus vaccine prototype in Vero cells: immunogenicity and protection in mice and rhesus monkeys.
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.
Putnak
R
R
Walter Reed Army Institute of Research, Division of Communicable Diseases and Immunology, Washington, DC 20307-5100, USA.
Barvir
D A
DA
Burrous
J M
JM
Dubois
D R
DR
D'Andrea
V M
VM
Hoke
C H
CH
Sadoff
J C
JC
Eckels
K H
KH
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
D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D005557:Formaldehyde