A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico

Abstract

This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [< 2 years], 26% [2-4 years], 60% [5-20 years], and 93% [21-50 years]). Safety profiles of TDEN vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858.

Figure 1.

Subject disposition. * Withdrawals through study Month 12. N = number of subjects; AE = adverse event; ATP = according to protocol.

Figure 2.

Pre-vaccination priming status, by age (total vaccinated cohort [TVC]).

Figure 3.

Reverse cumulative distribution curve for dengue virus (DENV) antibody titers at Month 7 for unprimed subjects (according to protocol [ATP] cohort for immunogenicity).

Figure 4.

Reverse cumulative distribution curve for dengue virus (DENV) antibody titers at Month 7 for primed subjects (according to protocol [ATP] cohort for immunogenicity).