Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines. Issue 24 (7th June 2018)

• Record Type: Journal Article
• Authors: Vannice, Kirsten S.; Wilder-Smith, Annelies; Barrett, Alan D.T.; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P.; Endy, Tim; Harris, Eva; Innis, Bruce L.; Katzelnick, Leah C.; Smith, Peter G.; Sun, Wellington; Thomas, Stephen J.; Hombach, Joachim
• Is Part Of: Vaccine. Volume 36:Issue 24(2018)
• Page Start: 3411
• Page End: 3417
• Publication Date: 2018-06-07
• Subjects: Dengue -- Dengue vaccine -- Vaccine clinical trials -- Vaccine regulation -- Enhancement; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.02.062
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Without immune correlates, dengue vaccine efficacy trials require clinical endpoints. Recent evidence impacts trial design and follow-up of 2 nd generation dengue vaccines. Vaccine safety and efficacy stratified by pre-vaccination serostatus is essential. Trial data should be interpreted with consideration of transient heterotypic immunity. Abstract: Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines.