Background: The live attenuated DEN1 vaccine candidate virus rDEN1Delta30 has been evaluated in preclinical animal models and found to be attenuated and immunogenic. These promising preclinical studies have identified rDEN1Delta30 as a candidate DEN1 vaccine virus for further testing in a human Phase I clinical trial.
Methods: rDEN1Delta30 at a dose of 10(3) pfu was administered as a single inoculation to twenty healthy adult volunteers. Eight additional volunteers received placebo. Volunteers were monitored closely for adverse events and serum was collected on study days 0, 28, 42 and 180 for determination of neutralizing antibody titer.
Results: The vaccine was well tolerated by the vaccinees. The most common adverse events observed were a transient asymptomatic rash in 40% of vaccinees and a mild neutropenia in 45% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic with 95% of vaccinees developing a > or =4-fold rise in serum neutralizing antibody titer against DEN1 that persisted throughout the six month duration of the trial.
Conclusions: The rDEN1Delta30 vaccine is safe and induced a potent and durable antibody response against DEN1. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.