Recent progress in dengue vaccine research and development

Recent data suggest that dengue immunity could be elicited via either humoral or cell-mediated routes. Directing the immune response to serotype-specific epitopes from domain (D) III of the dengue virus envelope protein (Env) may induce effective levels of neutralizing antibodies. Removing serotype-crossreactive epitopes from DIII, as well as DII, may reduce the potential for the vaccine to induce non-neutralizing antibodies associated with antibody-dependent enhancement (ADE) of infection. The use of consensus Env DIII sequences for each serotype, and perhaps even a single consensus sequence for all four serotypes of dengue virus, may direct the immune response to invariant neutralizing sequences, which might improve vaccine safety and long-term efficacy. Vaccines incorporating capsid and/or non-structural (NS) proteins may be capable of inducing tetravalent cell-mediated immunity without ADE. However, the potential of cell-mediated immunity to contribute to pathology is not well understood, and modifications of NS proteins, such as truncated NS1, may be necessary for optimal vaccine safety. This review discusses recent progress in the development of dengue vaccines.