Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

• Published in: Virology (New York, N.Y.) Vol. 314; no. 1; pp. 190 - 195
• Main Authors: Pletnev, Alexander G, Claire, Marisa St, Elkins, Randy, Speicher, Jim, Murphy, Brian R, Chanock, Robert M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2003
• Subjects: Animals; Antibodies, Viral - blood; Cercopithecus aethiops; Dengue virus; Dengue Virus - genetics; Dengue Virus - immunology; Dengue Virus - metabolism; Disease Models, Animal; Genetic Engineering - methods; Humans; Macaca mulatta; Neutralization Tests; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vero Cells; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Envelope Proteins - metabolism; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; West Nile Fever - prevention & control; West Nile virus; West Nile virus - genetics; West Nile virus - immunology; West Nile virus - metabolism
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/S0042-6822(03)00450-1

Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3′ noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3′Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3′Δ30, will be evaluated first in our initial clinical studies.