Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents

Biswal, Shibadas; Reynales, Humberto; Sáez-Llorens, Xavier; López, Pío; Borja-Tabora, Charissa; Kosalaraksa, Pope; Sirivichayakul, Chukiat; Watanaveeradej, Veerachai; Rivera, Luis; Espinoza, Félix; Fernando, LakKumar; Dietze, Reynaldo; Luz, Kléber Giovanni; Cunha, Rivaldo Venâncio da; Jimeno, J.; López‐Medina, Eduardo; Borkowski, Astrid; Brose, Manja; Rauscher, Martina; Lefevre, Inge; Bizjajeva, Svetlana; Bravo, Lulu; Wallace, Derek

doi:10.1056/nejmoa1903869

Cited by 230 publications

(237 citation statements)

References 11 publications

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“…No vaccine-related SAEs were reported and reactogenicity profiles of all formulations were consistent with those in previous reports of TAK-003. [12][13][14][15][16][20][21][22][23][24] The reasons for the differences in the magnitude of the immune responses between lyophilized and liquid formulations are unknown, but the immunological equivalence achieved for DENV-2 and DENV-4, as well as the limited differences in GMTs between IDT liquid and lyophilized formulations, suggest that the failure of equivalence for DENV-1 and DENV-3 is not related to the lyophilization process. Indeed, the elicited increases in GMTs and high levels of seropositivity to all serotypes achieved in this trial supported the further development of TAK-003 as a lyophilized vaccine.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of lyophilized and liquid dengue tetravalent vaccine candidate formulations in healthy adults: a randomized, phase 2 clinical trial

Turner

Papadimitriou

Winkle

et al. 2020

Human Vaccines & Immunotherapeutics

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Takeda has developed a live-attenuated dengue tetravalent vaccine candidate (TAK-003) which has been shown to be immunogenic with acceptable reactogenicity in phase 1 trials. In agreement with World Health Organization prequalification requirements for dengue vaccines, Takeda has manufactured a lyophilized formulation of TAK-003 that allows stable storage at +2°C to +8°C. This randomized, double-blind, phase 2 study (NCT02193087) was performed in 1002 healthy dengue-naïve adults, 18-49 years of age, across seven centers in the USA to compare the safety and immunogenicity of one or two doses of a lyophilized TAK-003 formulation with the liquid TAK-003 formulation used in previous phase 1 studies. The primary objective was to show immunologic equivalence in terms of geometric mean titers (GMT) of neutralizing antibodies to the four dengue serotypes one month after one dose of the lyophilized and liquid formulations. Secondary assessments were of safety and seropositivity rates, including after a second dose. The primary endpoint was not met, because immunologic equivalence after one dose was only shown for the DENV-2 serotype. Nonetheless, GMTs and seropositivity rates to all four serotypes were achieved with all formulations after two doses and are in line with what was observed in previous studies. Additionally, in view of the acceptable reactogenicity, with no vaccine-related serious adverse events reported, these data support continuing further clinical development of the lyophilized TAK-003 formulation.

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Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of lyophilized and liquid dengue tetravalent vaccine candidate formulations in healthy adults: a randomized, phase 2 clinical trial

Turner

Papadimitriou

Winkle

et al. 2020

Human Vaccines & Immunotherapeutics

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“…The WHO Global Vector Control Response (GVCR) initiative therefore recommended integrated approaches to address multiple vectors and vector-borne diseases [4]. Unfortunately, unlike malaria, for which effective prevention and treatment options are widely available, the Aedes-borne diseases still rely mostly on personal protection measures [5], even though vaccine trials are increasingly advanced [6].…”

Section: Introductionmentioning

confidence: 99%

Habitat characteristics and insecticide susceptibility of Aedes aegypti in the Ifakara area, south-eastern Tanzania

et al. 2020

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Background: Aedes-borne diseases such as dengue and chikungunya constitute constant threats globally. In Tanzania, these diseases are transmitted by Aedes aegypti, which is widely distributed in urban areas, but whose ecology remains poorly understood in small towns and rural settings. Methods:A survey of Ae. aegypti aquatic habitats was conducted in and around Ifakara, a fast-growing town in south-eastern Tanzania. The study area was divided into 200 × 200 m search grids, and habitats containing immature Aedes were characterized. Field-collected Ae. aegypti were tested for susceptibility to common public health insecticides (deltamethrin, permethrin, bendiocarb and pirimiphos-methyl) in the dry and rainy seasons. Results:Of 1515 and 1933 aquatic habitats examined in the dry and rainy seasons, 286 and 283 contained Aedes immatures, respectively (container index, CI: 18.9-14.6%). In the 2315 and 2832 houses visited in the dry and rainy seasons, 114 and 186 houses had at least one Aedes-positive habitat, respectively (house index, HI: 4.9-6.6%). The main habitat types included: (i) used vehicle tires and discarded containers; (ii) flowerpots and clay pots; and (iii) holes made by residents on trunks of coconut trees when harvesting the coconuts. Used tires had highest overall abundance of Ae. aegypti immatures, while coconut tree-holes had highest densities per habitat. Aedes aegypti adults were susceptible to all tested insecticides in both seasons, except bendiocarb, against which resistance was observed in the rainy season. Conclusions:To our knowledge, this is the first study on ecology and insecticide susceptibility of Ae. aegypti in Ifakara area, and will provide a basis for future studies on its pathogen transmission activities and control. The high infestation levels observed indicate significant risk of Aedes-borne diseases, requiring immediate action to prevent potential outbreaks in the area. While used tires, discarded containers and flowerpots are key habitats for Ae. aegypti, this study also identified coconut harvesting as an important risk factor, and the associated tree-holes as potential targets for Aedes control. Since Ae. aegypti mosquitoes in the area are still susceptible to most insecticides, effective control could be achieved by combining environmental management, preferably involving communities, habitat removal and insecticide spraying.

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“…However, the recommendation for extra safety precautions for this vaccine by the WHO (Sridhar et al, 2018) points to the limitation of its application. Another live-attenuated tetravalent dengue vaccine, TAK-003, from Takeda in Japan was reported to have positive top-line results from a very large Phase III trial (Biswal et al, 2019;Sharma et al, 2019;Tong, 2019). Nevertheless, developing efficacious vaccines against dengue with balanced immune responses, especially tetravalent protection, is of great necessity.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

Feng

Zheng

Wang

et al. 2020

Front. Cell. Infect. Microbiol.

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Dengue virus (DENV) is the causative agent of dengue, and its incidence has increased 30-fold in the past five decades. Among the four cocirculating serotypes, DENV3 is associated with an increased number of severe infections and has become widespread. Vaccination is the mainstay of prevention in reducing disease burden. Previously, the protective efficacy of DNA vaccine candidates toward DENV1, 2, and 4 was confirmed in mice. In this study, a DNA vaccine candidate (pVAX1-D3ME) expressing the prM and E proteins of DENV3 was constructed, and then the immunogenicity and protection were assessed in mice to further develop a tetravalent dengue vaccine. Moreover, the cross-reactive immune responses against the other three serotypes were investigated. The results showed that three doses of 50 µg of pVAX1-D3ME were sufficient to induce strong antigen-specific T cell responses and robust and consistent neutralizing antibodies. Additionally, immunization with pVAX1-D3ME offered protective immunity against not only DENV3 but also the other three serotypes, which could be observed even after 12 months. This study shows great promise for the further evaluation of a dengue tetravalent DNA vaccine candidate in large animal models, including non-human primates.

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Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents

Cited by 230 publications

References 11 publications

Immunogenicity and safety of lyophilized and liquid dengue tetravalent vaccine candidate formulations in healthy adults: a randomized, phase 2 clinical trial

Immunogenicity and safety of lyophilized and liquid dengue tetravalent vaccine candidate formulations in healthy adults: a randomized, phase 2 clinical trial

Habitat characteristics and insecticide susceptibility of Aedes aegypti in the Ifakara area, south-eastern Tanzania

Long-Term Protection Elicited by a DNA Vaccine Candidate Expressing the prM-E Antigen of Dengue Virus Serotype 3 in Mice

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