A tetravalent live-attenuated 3-dose
vaccine composed of chimeras of
yellow fever 17D and the four dengue viruses (CYD, also called
Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that
vaccine be administered to >/ = 9 year-olds residing in highly
dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose,
vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough
dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that
dengue NS1
IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received
Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later,
dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering
Dengvaxia predicted by the manufacturer, WHO and others derive from scoring
dengue hospitalizations of vaccinated children as
vaccine failures rather than as
vaccine enhanced
dengue disease. Recommended regimens for administration of
Dengvaxia should have been structured to warn of and avoid serious adverse events.