Vaccine Research  
There is no vaccine to protect against dengue. Although progress is underway, developing a vaccine against the disease is challenging. With four different serotypes of the dengue virus that can cause the disease, the vaccine must immunize against all four types to be effective. Vaccination against only one serotype could possible lead to severe DHS when infected with another serotype due to Antibody-Dependent Enhancement. There is still limited knowledge of how the disease typically behaves and how the virus interacts with the immune system. Another difficulty is that there is no reliable animal model for DHF and thus also not a suitable animal model to test immune responses to potential vaccines. In addition, progress in vaccine development is slow mainly because dengue viruses grow poorly in cell culture (see also Clinical Trials).
As there is no cross-protection between the four dengue serotypes, and because of the possibility of immune enhancement by monotypic antibody leading to DHF with subsequent natural infections, the control of dengue will be possible only after an efficient tetravalent vaccine has been developed. This means a vaccine that protects against all four dengue serotypes. The most favored strategy is to develop a live vaccine. Attenuation was obtained by repeated passage of wild-type strains of dengue viruses in cell culture. The difficulty in this approach has been to find the correct balance between insufficient attenuation and over-attenuation of the candidate vaccine strains, as criteria of virus attenuation in vitro, such as small plaque phenotype and temperature-sensitive growth, do not appear to be predictive of attenuation in vivo. In addition, whereas monovalent attenuated vaccine lots showed good immunogenicity, their combination into a tetravalent vaccine initially generated disappointing immunogenicity results, due to a phenomenon of interference between strains. Other approaches for vaccine development include inactivated and subunit vaccines, DNA vaccines and recombinant vaccinia virus (MVA) vectors. Most advanced are efforts to develop a subunit, tetravalent vaccine using a mixture of the E protein from the four dengue serotypes and the nonstructural NS1 protein of DV-2 as immunogens in a proprietary adjuvant.
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