Volume 35, Issue 27, Pages 3431-3514 (14 June 2017)
Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?
Bradford D. Gessner, Neal Halsey
A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2–5 years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2–5 years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1–2 to years 3–5 of follow-up for all age groups and regions.