The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study.

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV-Sanofi Pasteur) and DENVax (TAK 003-Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.