Safety and Immunogenicity of a Rederived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults Living in Thailand: A Randomized Trial

Abstract

Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial (NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.

Controlling Dengue: Effectiveness of Biological Control and Vaccine in Reducing the Prevalence of Dengue Infection in Endemic Areas

“…The development of DENV vaccines should encompass all the serotypes present in order for it to be successful [ [50]. A multivalent vaccine is important in dengue virus treatment as a vaccine that targets one serotype will only be specific to that serotype viral structures but not others [11] [36] [50] [52]. In an endemic area, a person can be infected with either one serotype or multiple serotypes of DENV [11] [36] [50] [52].…”

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.…”

Vaccines and immunization strategies for dengue prevention

“…31, 32, 33 Recently, an advanced formulation named TDEN-F17/F19 based on the above-mentioned live attenuated viruses was developed for a new cycle of clinical assessment and exhibited sufficient safety and immunogenicity in two phase II clinical studies. 34, 35 In addition to virus attenuation by serial passaging, the virulence of these new vaccine strains was reduced by manipulation of their viral genome. 35 …”

“…34, 35 In addition to virus attenuation by serial passaging, the virulence of these new vaccine strains was reduced by manipulation of their viral genome. 35 …”