Phase 1 randomized study of a tetravalent dengue purified inactivated vaccine in healthy adults in the United States

Abstract

The safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01E or AS03B), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18-39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo. The response to a third dose was evaluated in a subset of nine participants remote from primary vaccination. Humoral immunogenicity was assessed using a 50% microneutralization assay. All DPIV formulations were well tolerated. No vaccine-related serious adverse events were observed through 12 months after the second vaccine dose. In all DPIV groups, geometric mean antibody titers peaked at Day 56, waned through 6 months after the second vaccine dose, and then stabilized. In the nine subjects where boosting was evaluated, a strong anamnestic response was observed. These results support continuation of the clinical development of this dengue vaccine candidate (clinicaltrials.gov: NCT01666652).