Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

Abstract

Objective. To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). Methods. Participants aged 12–17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. Results. 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). Conclusion. TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Dengue Fever Epidemics and the Prospect of Vaccines: A Systematic Review and Meta-Analysis Using Clinical Trials in Children

“…The risk of bias analysis using the Cochrane Collaboration tool [28] revealed that among the 32 randomized controlled trial (RCT) studies, 25 articles were rated as low risk in the following domains (information, confounding, selection, attrition, and reporting biases): [31,34,36,[38][39][40][43][44][45][46][47][50][51][52][54][55][56][57]59,[62][63][64][65][66][67]. Conversely, seven studies were rated as having "some concerns" about the risk of bias because of insufficient detailed information on the randomization process, such as blinding and concealment [30,32,33,53,58,60,61]. The risk of bias domains for each of the studies is displayed in Figure 2.…”

Controlled Human Infection Models To Accelerate Vaccine Development

“…It is constructed from a cDNA clone of a DENV-2 strain attenuated through serial passage in dog kidney cells in culture, into which prM and E genes of the other three dengue serotypes were cloned. TAK-003 (and various precursor formulations, admixtures of the four-component attenuated DENV strains, and dose regimens) were tested in at least nine studies in healthy, dengue-naïve adult and adolescent volunteers in the United States, Mexico, and Colombia as well as in both adults and children in dengue-endemic countries in Asia and Latin America (151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161). Collectively, these studies found that one or two doses induced a tetravalent neutralizing antibody response ranging from 60 to 97 percent of subjects, depending on previous dengue exposure.…”

Insight parameter drug design for human beta-tryptase inhibition integrated molecular docking, QSAR, molecular dynamics simulation, and pharmacophore modelling studies of alpha-keto-[1,2,4]-oxadiazoles

“…However, the efficacy of Dengvaxia® vaccination is varied across different serotypes, ages, and status of dengue sera before vaccination [5], [6]. Besides, the WHO Strategic Advisory Panel has recommended the use of Dengvaxia® for dengue-seropositive patients only because it has been found to increase the risk of severe dengue in seronegative individuals [5], [6]. To date, dengue treatment has relied on the management of clinical signs and symptoms, including the prescription of non-steroidal anti-inflammatory agents (NSAIDs), clinical parameters tracking, and fluid management to stabilise hemodynamic status [7].…”

“…At the time of writing, Dengvaxia® (Sanofi Pasteur) is the only dengue vaccine that has been approved for use in people over nine years old in around 20 countries worldwide since it was first licensed in Mexico in 2015 [5], [6]. However, the efficacy of Dengvaxia® vaccination is varied across different serotypes, ages, and status of dengue sera before vaccination [5], [6]. Besides, the WHO Strategic Advisory Panel has recommended the use of Dengvaxia® for dengue-seropositive patients only because it has been found to increase the risk of severe dengue in seronegative individuals [5], [6].…”

“…The primary prevention method of dengue is vector control, while medications and effective vaccines for dengue are still under development. At the time of writing, Dengvaxia® (Sanofi Pasteur) is the only dengue vaccine that has been approved for use in people over nine years old in around 20 countries worldwide since it was first licensed in Mexico in 2015 [5], [6]. However, the efficacy of Dengvaxia® vaccination is varied across different serotypes, ages, and status of dengue sera before vaccination [5], [6].…”