A Phase II, Randomized, Safety and Immunogenicity Study of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults

Abstract

Two formulations of a new live tetravalent dengue virus (DENV) vaccine produced using re-derived master seeds from a precursor vaccine and that same precursor vaccine as a control were compared in a placebo-controlled, randomized, observer-blind, phase II trial of 86 healthy adults. Two vaccine doses were administered 6 months apart; a third dose was offered to a subset. Symptoms and signs of dengue-like illness reported after vaccination were mild to moderate, transient, and occurred with similar frequency among recipients of the new DENV vaccine and placebo, except for rash. Neither dengue nor vaccine-related serious adverse events were reported. The first DENV vaccine dose was moderately immunogenic; the second dose increased the potency and breadth of the neutralizing antibody response. Tetravalent response rates to the new formulations were 60% and 66.7% in unprimed subjects. A third dose did not increase tetravalent antibody rates. The new DENV vaccine candidates merit additional evaluation.

“Current Dengue Vaccine Status”

“…Instances of DENV-4 viremia were less among those who received the re-derived vaccine candidate (one subject, flavivirus naïve, asymptomatic) compared to the nonre-derived candidate (five subjects, four were flavivirus naïve, four with symptomatic viremia). During the follow up phase, physical examinations, clinical laboratory determinations, and lack of symptomatic viremia all support the acceptable safety profile of the new vaccine candidate [48]. In the Thai study, asymptomatic, low level viremia (DENV-2, DENV-3 or DENV-4) was detected in five of 80 vaccine recipients.…”

“…Vaccination was well tolerated with an acceptable safety profile in all groups in all studies. Tetravalent seroconversion rates in flavivirus naïve, U.S. volunteers after two doses administered on a 0 and 6 month schedule ranged from 60 % to 66.7 % [48]. Instances of DENV-4 viremia were less among those who received the re-derived vaccine candidate (one subject, flavivirus naïve, asymptomatic) compared to the nonre-derived candidate (five subjects, four were flavivirus naïve, four with symptomatic viremia).…”

Trials and tribulations on the path to developing a dengue vaccine

“…Newly derived vaccine lots produced in collaboration with GlaxoSmithKline Vaccines (GSK) were tested in adults in the United States (U.S.), Thailand and in Puerto Rico across a broad age range (12 months to 50 years) using two doses of vaccine delivered SQ at days 0 and 180 [80,81]. Long term follow up (up to 5 years) and administration of a 3rd dose of vaccine to children in Thailand vaccinated with a first generation tetravalent formulation has been completed.…”

Immunogenicity of a Candidate DNA Vaccine Based on the <i>prM/E</i> Genes of a Dengue Type 2 Virus Cosmopolitan Genotype Strain

“…Vaccination is a preventative method that may prove successful, as it has with other infectious diseases (3). Several dengue vaccine candidates are being developed using different approaches, such as live attenuated (4)(5)(6)(7)(8), chimeric (8)(9)(10), recombinant subunit (8,(11)(12)(13)(14), and DNA vaccines (8,(15)(16)(17)(18)(19).…”