rDEN4σ30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers

Abstract

Background. The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4Δ30 was previously found to be safe and immunogenic at a dose of 105 plaque-forming units (pfu). Methods. In a follow-up placebo-controlled phase 2 clinical trial, rDEN4Δ30 was administered as a single inoculation to 3 separate dose cohorts (103 pfu, 10 2 pfu, or 101 pfu), for further evaluation. Each dose cohort consisted of 20 vaccines and 4 placebo recipients. Volunteers were monitored closely for adverse events, and serum was collected on study days 28 and 42 for determination of neutralizing antibody titer. Results. The vaccine was well tolerated at all doses studied. The most common adverse events observed were a transient asymptomatic rash in >50% of vaccinees and a mild neutropenia in ∼20% of vaccinees. No vaccinee developed a dengue-like illness. The vaccine was highly infectious and immunogenic, with 95%-100% of vaccinees in each dose cohort developing a ≥4-fold increase in titers of serum neutralizing antibodies against DEN-4. Conclusions. The rDEN4Δ30 vaccine is safe and induced an antibody response that was broadly neutralizing against genotypically diverse DEN-4 viruses. It is a promising vaccine candidate for inclusion in a tetravalent dengue vaccine formulation.