Dengue is a rapidly emerging mosquito-borne viral infection of humans, with an estimated 2.5 billion people at risk worldwide. It has been estimated that the dengue viruses (DENVs) cause 50-100 million clinically apparent infections and up to 50,000 deaths each year.
After more than 70 years of effort, a successful DENV vaccine remains an elusive goal but several research groups are currently evaluating live attenuated DENV vaccine candidates in Phase 2 and Phase 3 clinical trials. So far, major obstacles for the development of live virus vaccines include low seroconversion rates, prolonged immunization schedules, and sometimes, vaccine reactogenicity
As an alternative, non-replicating vaccines are being pursued that could potentially shorten the dosing schedule and provide a safer preparation that can be administered to children, chronically ill, or immunosuppressed individuals. To date, DENV purified inactivated vaccines (PIV) have shown high immunogenicity and protection over the short term, but have been poor at inducing cell-mediated immune responses and long-term protection.
The dengue nonstructural protein 3 (NS3) is considered the main target for T-cell responses during viral infection. Navy researchers believe that the addition of the DENV NS3, which is a potent stimulator of cell-mediated immunity, might significantly improve the efficacy of the PIV vaccine and provide longer-term protection.
To prove this out, they have incorporated recombinant subunit NS3 proteins representing protease and/or helicase as components of the DENV-2 serotype PIV vaccine to determine if they generate better T-cell responses than the DENV PIV vaccine alone.
Initial studies in mice have resulted in the novel finding that the addition of recombinant NS3 helicase domain to a killed DENV vaccine can increase virus-specific antibody and neutralizing antibody titers, as well as elicit cell-mediated immune responses. The results indicate that incorporating recombinant NS3 helicase protein as a component of the DENV-2 PIV may synergistically generate a more effective immune response.
The patent available for reference relates to pharmaceutical compositions comprising a nucleic acid sequence encoding an NS3 helicase polypeptide (or fragments) and adjuvants sufficient to produce an enhanced immune response to the purified whole inactivated dengue virus immunogenic composition.
- A more effective purified inactivated dengue virus vaccine that may stimulate humoral as well as cell-mediated immunity
- Effective against all four antigenically related serotypes
- US patent 10,105,434 available for license