The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries

Background: With approximately 3 billion people at risk of acquiring the infection, dengue fever is now considered the most important mosquito-borne viral disease in the world, with 390 million dengue infections occurring every year, of which 96 million manifest symptoms with any level of disease severity. Treatment of uncomplicated dengue cases is only supportive and severe dengue cases require hospital intensive care. A vaccine now licensed in several countries and developed by Sanofi Pasteur (CYD-TDV, named Dengvaxia), was able to protect, in the first 25 months of the two Phase III, 66% of a subset of 9–16 year old participants. However, a significantly lower efficacy (including negative vaccine efficacy) was noted for children younger than 9 years of age. Methodology/Principal Findings: Analysis of year 3 results of phase III trials of Dengvaxia suggest high rates of protection of vaccinated partial dengue immunes but high rates of hospitalizations during breakthrough dengue infections of persons who were vaccinated when seronegative, with vaccine appearing to induce enhancing antibodies (ADE). An age structured model was developed based on Sanofi’s recommendation to vaccinate persons age 945 years in dengue endemic countries. The model was used to explore the clinical burden of two vaccination strategies: 1) Vaccinate 4 or 20% of individuals, ages 9–45 years, seropositives and seronegatives, and 2) vaccinate 4 or 20% of individuals, ages 9–45 years, who are dengue immune only. Conclusions/Significance: Our results show that vaccinating dengue monotypic immune individuals prevents dengue hospitalizations, but at the same time dengue infections of vaccine-sensitized persons increases hospitalizations. When the vaccine is given only to partial immune individuals, after immunological screening of the population, disease burden decreases considerably. Author Summary: Caused by four antigenically related but distinct serotypes a tetravalent vaccine is needed to protect against the huge burden of dengue disease. Dengvaxia is a vaccine candidate now licensed in several countries for individuals 9–45 years of age living in endemic countries with at least 50% (preferably 70%) of seroprevalence. Modelers from Sanofi Pasteur have predicted that this vaccine has the potential to reduce by about 50% the disease burden within 5 years when 20% of an endemic country population is vaccinated, thus achieving a World Health Organization dengue prevention goal. In this paper, mathematical modeling is used to investigate the impact of the newly licensed dengue vaccine using different scenarios. Our results show that to achieve significant reduction in disease burden, the vaccination program is most effective if it includes only individuals that have been already exposed to at least one dengue virus. Immunological screening of the population prior to vaccination is advised and vaccination strategies must be planned based on epidemiological disease dynamics for each specific endemic region.