Generating flavivirus vaccine candidates by modulating interferon sensitivity

Abstract

Evaluation of: Liang JJ, Liao CL, Liao JT, Lee YL, Lin YL. A Japanese encephalitis virus vaccine candidate strain is attenuated by decreasing its interferon antagonistic ability. Vaccine 27(21), 2746–2754 (2009).Flavivirus infections are currently emerging or re-emerging, which increases the need for efficient vaccination. Among the medically important flaviviruses, Japanese encephalitis virus infection has the highest mortality rate and is a major public-health problem in parts of Asia. Traditionally, attenuated vaccine candidates are developed by repeated passage or random mutagenesis. Defining the mechanisms underlying attenuation can lead to more sophisticated development of vaccine candidates. The paper under evaluation describes the potential mechanisms leading to attenuation of the original virulent strain. The authors found that the virus’s decreased ability to counteract the antiviral interferon response is the major attenuation determinant and this finding paves the way for the use of this virus as a prospective vaccine candidate. These results indicate that vaccine candidates can be developed by introducing targeted mutations to disrupt motifs in proteins responsible for inhibition of the interferon response.