Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA
ABSTRACT A candidate recombinant, live-attenuated, CYD tetravalent dengue vaccine (CYD-TDV) has recently demonstrated immunogenicity, efficacy and good tolerability. This study was performed to evaluate three CYD-TDV formulations in adults.
This was a randomized, double-blind, multicenter, phase II trial. The vaccine formulations were: CYD-TDV 5555 (≈5log10 tissue culture infectious dose 50% [TCID50] of serotypes 1-4); CYD-TDV 5553 (≈5log10 TCID50 of serotypes 1-3 and ≈3log10 TCID50 of serotype 4); and CYD-TDV 4444 (≈4log10 TCID50 of serotypes 1-4). Vaccinations were administered at 0, 6 and 12 months. Immunogenicity was assessed using the plaque reduction neutralization test.
In total, 260 individuals were enrolled. The 5555 formulation elicited a superior serotype 4 response versus the 5553 formulation, with seropositivity rates of 89.7% and 58.3%, respectively, after the second dose (between-group difference 31.4%; 95% confidence interval 18.2-43.2). After each of the three doses, seropositivity rates for serotypes 1-3 were numerically highest with CYD-TDV 5553 and lowest with the 4444 formulation; seropositivity rates for serotype 4 were similar with the 5555 and 4444 formulations, and much lower among recipients of CYD-TDV 5553. Geometric mean titers followed the same pattern as that seen with seropositivity rates. Safety/reactogenicity results were similar for all three vaccine formulations, although the percentage of participants reporting solicited injection site reactions was lower with CYD-TDV 4444 than with the other two formulations. All serious adverse events were unrelated to vaccination.
Reducing the dose of serotype 4 antigen (5553 formulation) creates an imbalance in the immune response to CYD-TDV. Immune responses to CYD-TDV 5555 were slightly higher than to the 4444 formulation. Development of CYD-TDV 5555 has subsequently been pursued.
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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 American journal of tropical medicine and hygiene 11/2013; 89(6). DOI:10.4269/ajtmh.13-0304 · 2.74 Impact Factor
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ABSTRACT: The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.Human Vaccines & Immunotherapeutics 02/2014; 10(5). DOI:10.4161/hv.28117 · 3.64 Impact Factor
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ABSTRACT: An estimated 100 million people have symptomatic dengue infection every year. This is the first report of a phase 3 vaccine efficacy trial of a candidate dengue vaccine. We aimed to assess the efficacy of the CYD dengue vaccine against symptomatic, virologically confirmed dengue in children.The Lancet 07/2014; 384(9951). DOI:10.1016/S0140-6736(14)61060-6 · 45.22 Impact Factor