Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN4Δ30-4995 in Healthy Adult Volunteers

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Abstract
RDEN4Δ30-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine candidate specifically designed as a further attenuated derivative of the rDEN4Δ30 parent virus. In a previous study, 5 of 20 vaccinees who received 105 plaque-forming units (PFU) of rDEN4Δ30 developed a transient elevation of the serum alanine aminotransferase (ALT) level and an asymptomatic maculopapular rash developed in 10 of 20. In the current study, 28 healthy adult volunteers were randomized to receive 105 PFU of rDEN4Δ30-4995 (20) or placebo (8) as a single subcutaneous injection. The vaccine was safe, well-tolerated, and immunogenic. An asymptomatic generalized maculopapular rash and elevations in ALT levels were observed in 10% of the rDEN4Δ30-4995 vaccinees. None of the rDEN4Δ30-4995 vaccinees became viremic, yet 95% developed a four-fold or greater increase in neutralizing antibody titers. Thus, rDEN4Δ30-4995 was demonstrated to be safe, highly attenuated, and immunogenic. However, an asymptomatic localized erythematous rash at the injection site was seen in 17/20 rDEN4Δ30-4995 vaccinees. Therefore, alternative DENV4 vaccine strains were selected for further clinical development.