Recent progress on sanofi pasteur's dengue vaccine candidate.

The sanofi pasteur candidate dengue tetravalent vaccine (TV) is a recombinant live attenuated vaccine. It is based on a backbone of yellow fever vaccine (YF 17D) replication genes and incorporates the envelope genes of the four dengue virus serotypes. Pre-clinical studies have demonstrated that dengue TV is genetically stable, non-hepatotropic, less neurovirulent than YF 17D and does not infect mosquitoes by the oral route. Dengue TV reactogenicity, viraemia induction and antibody responses were investigated in three Phase II trials in the USA, the Philippines and Mexico. Participants were randomised to receive a three-dose regimen of dengue TV over 12 months (given at baseline, 3-4 and 12 months) or a control vaccine/placebo at baseline followed by two injections of dengue TV. Results showed that the majority of adverse events were mild to moderate and transient in nature, while no evidence of induction of viraemia was reported after initial dengue TV administration. Seroconversion was 100% for all four serotypes in flavivirus-naive adults in the USA injected with dengue TV. Similarly, seroconversion was 88-100% following three administrations in flavivirus-naive Mexican children aged 2-5 years. Furthermore, the proportion of seropositive subjects increased with each dengue TV injection in the Philippines where baseline flavivirus immunity was high (80.1%). An extensive clinical development programme for dengue TV is underway including an efficacy trial in Ratchaburi province, Thailand (an area of high dengue incidence). Assuming continued successful outcomes, initial submissions to regulatory authorities are envisaged within a 5-year period.