rDEN4 Delta 30, a Live Attenuated Dengue Virus Type 4 Vaccine Candidate, Is Safe, Immunogenic, and Highly Infectious in Healthy Adult Volunteers

Background. The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4 Delta 30 was previously found to be safe and immunogenic at a dose of 10 super(5) plaque-forming units (pfu). Methods. In a follow-up placebo-controlled phase 2 clinical trial, rDEN4 Delta 30 was administered as a single inoculation to 3 separate dose cohorts (10 super(3) pfu, 10 super(2) pfu, or 10 super(1) pfu), for further evaluation. Each dose cohort consisted of 20 vaccinees 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 similar to 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 greater than or equal to 4-fold increase in titers of serum neutralizing antibodies against DEN-4. Conclusions. The rDEN4 Delta 30 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.