Immunogenicity and Safety of a Recombinant Tetravalent Dengue Vaccine in Children and Adolescents Ages 9–16 Years in Brazil

Abstract

Immunogenicity and safety of a recombinant, live-attenuated, tetravalent dengue disease vaccine (CYD-TDV) was evaluated in children/adolescents in Brazil. In this observer-blind, placebo-controlled, phase II single-center study, children/adolescents (ages 9–16 years) were randomized to receive CYD-TDV or placebo at 0, 6, and 12 months. Immunogenicity was assessed using a 50% plaque neutralization test. Overall, 150 participants were enrolled (CYD-TDV: N = 100; placebo: N = 50). Injection site pain and headache were the most common solicited injection site and systemic reactions. Unsolicited adverse events (AEs) and serious AEs were similar between groups. No serious AEs were vaccine-related. Geometric mean titers against all dengue virus serotypes increased with CYD-TDV vaccination and were 267, 544, 741, and 432 1/dil for serotypes 1–4, respectively, after dose 3, representing a mean fold increase from baseline of 5, 6, 6, and 20, respectively. CYD-TDV vaccination elicited a neutralizing antibody response against serotypes 1–4 and was well-tolerated in children/adolescents in a dengue-endemic region.

The yellow fever 17D virus as a platform for new live attenuated vaccines

“…Early in 2011, the vaccine was administered to over 6000 children and adults from endemic and non-endemic areas with no questions regarding its safety. 41,42,46 A phase IIb clinical trial in 2669 Thai schoolchildren with the tetravalent vaccine showed poor efficacy (30.3%) of protection against febrile DEN infections. 45 While vaccination reduced incidence of DEN1, DEN3, and DEN4 by 90%, the protection against DEN2 was low (9.2%), downgrading overall protection.…”

“…39 These recombinant live attenuated chimeric viruses have been tested in man to different extents, and due to the inexistence of any alternative, particular attention has been devoted to the immunogenicity and safety of the YF17D-DV tetravalent vaccine. [40][41][42][43][44][45][46] The live attenuated chimeric 17D-DEN tetravalent vaccine candidate from Sanofi-Pasteur constitutes the most tested dengue vaccine possibility. The chimeric viruses proved to be genetically and phenotypically stable, 47 less virulent when compared with the yellow fever vaccine 17D and unable to infect mosquitoes orally.…”

Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine

“…To date, only neutralizing antibody levels (PRNT 50 ) have been determined in some TDV vaccine recipients using Vero cells, which do not express Fcc receptors. [113][114][115][116] An ADE assay should probably also be included in the evaluation of future dengue vaccines.…”

Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: A randomised study

“…Consistency studies are routinely undertaken for new biological products [20]. We conducted this lot-to-lot consistency study in people living in dengue-free areas of Australia in order to minimise the risk that natural infections would impact the assessment of the immune response following 3 doses of vaccine or placebo, approximately 13 months after vaccination commenced [10,[21][22][23].…”