Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment

Abstract

The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe "secondary-like" infection and, thus, the numbers hospitalized for dengue. In moderate transmission settings, we predict positive impacts overall but increased risks of hospitalization with dengue disease for individuals who are vaccinated when seronegative. However, in high-transmission settings, vaccination benefits both the whole population and seronegative recipients. Our analysis can help inform policy-makers evaluating this and other candidate dengue vaccines.

Fig. 1. Model fit to publicly available data from the Asian phase 3 clinical trial

See (6). Modal (best-fit) estimate and 95% credible intervals for four conditions. (A) proportion of participants of the immunological subset of the trial who were seronegative at the time of receiving their first dose, by age. (B) Attack rate of virologically confirmed symptomatic dengue in immunological subset in first two years after dose 1 by trial arm and baseline serostatus. (C) Attack rate of virologically confirmed symptomatic dengue in all trial participants in first two years after dose 1 by trial arm and age group. (D) Attack rate of virologically confirmed hospitalization with dengue disease in all trial participants in third year after dose 1 (first year of long-term follow-up) by trial arm and age group. Fit to Latin American trial shown in SM (10).

Fig. 2. Predicted population effects of vaccination on dengue disease for a range of transmission intensities (x axes) and ages of vaccination (y axes)

Color scale indicates proportion of cases averted in the whole population (A) over 10 years, for all symptomatic dengue; (B) over 10 years, for participants hospitalization with dengue; (C) over 30 years, for all symptomatic dengue; and (D) over 30 years, for hospitalization with dengue. Negative proportions of cases averted indicate vaccination increases risk. Solid contours indicate the optimal age of vaccination for each transmission intensity. Dashed contours indicate the youngest age group that may be targeted to avoid negative effects at the population level.

Fig. 3. Predicted individual effects of vaccination over 30 years

Proportion of hospitalized cases averted among individual vaccine recipients who are vaccinated: (A) when seronegative and (B) when seropositive. Dashed contour indicates the youngest age group that may be targeted to avoid negative effects at the individual level. (C) Minimum proportion of the age group (1-year age band) targeted for routine vaccination that should be seropositive before introduction of vaccination to avert negative impacts (over a 30-year time frame) at the population (red) and individual (blue) level.

Fig. 4. Expected population effects of vaccination if vaccination is preceded by serological testing (with a rapid test assumed to have 90% sensitivity and specificity) and only individuals who test seropositive for dengue are vaccinated

For the population, 80% coverage is assumed. (A) Proportion of hospitalizations averted over a 30-year period for different transmission intensities and target age at vaccination. (B) Proportion of vaccine doses saved (y axis) if only seropositive individuals are targeted, for different transmission intensities (x axis) and target ages (different curves).