Effectiveness of the TAK-003 Dengue Vaccine in Preventing Dengue Infection in Children: A Systematic Review
DOI:
https://doi.org/10.53366/jimki.v12i3.931Keywords:
children, dengue vaccine , efficacy, safety, TAK-003Abstract
BACKGROUND: Dengue fever remains an important global health issue, particularly among children. Developing an effective and safe vaccination against all four dengue virus serotypes is still a challenge. TAK-003 is a tetravalent vaccination candidate based on a live attenuated DENV-2 virus with great efficacy and a favorable safety profile.
METHOD: This systematic review was conducted using the PRISMA 2020 guidelines and a literature search of the PubMed, Scopus, and Wiley databases until October 15, 2025. Clinical trials and observational studies evaluating TAK-003's efficacy and safety in children were among the inclusion criteria. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale.
RESULTS: Out of 132 publications evaluated, four unique studies (2 RCTs, 1 single-arm study, and 1 case-control trial) fulfilled the inclusion criteria. A phase III clinical trial (NCT02747927) of 20,099 children aged 4 to 16 years found an overall vaccination effectiveness of 73.3% against symptomatic dengue, with the strongest protection against DENV-2 (95.1%) and DENV-1 (69.8%). Follow-up results for up to 4.5 years after vaccination showed continuous long-term efficacy, including protection in people seronegative for DENV-1 and DENV-2.
CONCLUSION: TAK-003 has been found to be safe, immunogenic, and effective in avoiding symptomatic and severe dengue in children and adolescents living in both endemic and non-endemic countries. This vaccine has tremendous potential as a global dengue preventive strategy, while protection against DENV-3 and DENV-4 need further improvement.
References
1. Deng J, Zhang H, Wang Y, Liu Q, Du M, Yan W, et al. Global, regional, and national burden of dengue infection in children and adolescents: an analysis of the Global Burden of Disease Study 2021. EClinicalMedicine. 2024 Dec 1;78.
2. WHO. World Health Organization. 2025. p. 1–5 Dengue Key Facts.
3. Nusrat N, Chowdhury K, Sinha S, Mehta M, Kumar S, Haque M. Clinical and Laboratory Features and Treatment Outcomes of Dengue Fever in Pediatric Cases. Cureus. 2024 Dec 17;
4. Tejo AM, Hamasaki DT, Menezes LM, Ho YL. Severe dengue in the intensive care unit. Vol. 4, Journal of Intensive Medicine. Chinese Medical Association; 2024. p. 16–33.
5. CDC. Centers for Disease Control and Prevention. 2025. p. 10–5 About Dengue Vaccine.
6. Anumanthan G, Sahay B, Mergia A. Current Dengue Virus Vaccine Developments and Future Directions. Vol. 17, Viruses. Multidisciplinary Digital Publishing Institute (MDPI); 2025.
7. Biswal S, Reynales H, Saez-Llorens X, Lopez P, Borja-Tabora C, Kosalaraksa P, et al. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. New England Journal of Medicine. 2019 Nov 21;381(21):2009–19.
8. Biswal S, Galvan JFM, Parra MM, Galan-Herrera JF, Rodriguez MBC, Bueno EPR, et al. Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City. Revista Panamericana de Salud Publica/Pan American Journal of Public Health. 2021;45.
9. Tricou V, Sáez-Llorens X, Yu D, Rivera L, Jimeno J, Villarreal AC, et al. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2–17 years: a randomised, placebo-controlled, phase 2 trial. The Lancet. 2020 May 2;395(10234):1434–43.
10. Biswal S, Borja-Tabora C, Martinez Vargas L, Velásquez H, Theresa Alera M, Sierra V, et al. Efficacy of a tetravalent dengue vaccine in healthy children aged 4–16 years: a randomised, placebo-controlled, phase 3 trial. The Lancet. 2020 May 2;395(10234):1423–33.
11. Sáez-Llorens X, Biswal S, Borja-Tabora C, Fernando LK, Liu M, Wallace D, et al. Effect of the Tetravalent Dengue Vaccine TAK-003 on Sequential Episodes of Symptomatic Dengue. American Journal of Tropical Medicine and Hygiene. 2023 Apr 1;108(4):722–6.
12. Tricou V, Yu D, Reynales H, Biswal S, Saez-Llorens X, Sirivichayakul C, et al. Long-term efficacy and safety of a tetravalent dengue vaccine (TAK-003): 4·5-year results from a phase 3, randomised, double-blind, placebo-controlled trial [Internet]. Vol. 12, www.thelancet.com/lancetgh. 2024. Available from: www.thelancet.com/lancetgh
13. Sirivichayakul C, Biswal S, Saez-Llorens X, López-Medina E, Borja-Tabora C, Bravo L, et al. Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination. Journal of Infectious Diseases. 2024 Dec 15;230(6):e1214–25.
14. Borja-Tabora C, Fernando LK, Lopez Medina E, Reynales H, Rivera L, Saez-Llorens X, et al. Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group. Clinical Infectious Diseases. 2025 Jan 15;80(1):199–206.
15. El Hindi T, Alera MT, Bravo L, Moreira ED, Dietze R, Oliveira AL, et al. Estimated Efficacy of TAK-003 Against Asymptomatic Dengue Infection in Children and Adolescents Participating in the DEN-301 Trial in Asia Pacific and Latin America. Journal of Infectious Diseases. 2025 Jun 15;231(6):e1160–9.
16. Fernando L, Kastner R, Wickramasinghe P, Fernando AD, Gunasekera D, Nguyen VH, et al. Role of the dengue vaccine TAK-003 in an outbreak response: Modeling the Sri Lanka experience. PLoS Negl Trop Dis. 2024 Aug 1;18(8).
17. Mandaric S, Friberg H, Saez-Llorens X, Borja-Tabora C, Biswal S, Escudero I, et al. Long term T cell response and safety of a tetravalent dengue vaccine in healthy children. NPJ Vaccines. 2024 Dec 1;9(1).
18. Ranzani OT, Lazar Neto F, Mareto LK, Brumatti TS, de Oliveira RD, da Silva PV, et al. Effectiveness of the TAK-003 dengue vaccine in adolescents during the 2024 outbreak in São Paulo, Brazil: a test-negative, case–control study. Lancet Infect Dis. 2025;
19. Petri E, Biswal S, Lloyd E, Tricou V, Folschweiller N. Early onset of protection of the TAK-003 dengue vaccine: Data from the DEN-301 clinical trial. Vaccine. 2024 Dec 2;42(26).
20. Patel SS, Winkle P, Faccin A, Nordio F, LeFevre I, Tsoukas CG. An open-label, Phase 3 trial of TAK-003, a live attenuated dengue tetravalent vaccine, in healthy US adults: immunogenicity and safety when administered during the second half of a 24-month shelf-life. Hum Vaccin Immunother. 2023;19(2).
21. LeFevre I, Bravo L, Folschweiller N, Medina EL, Moreira ED, Nordio F, et al. Bridging the immunogenicity of a tetravalent dengue vaccine (TAK-003) from children and adolescents to adults. NPJ Vaccines. 2023 Dec 1;8(1).
22. Rivera L, Biswal S, Sáez-Llorens X, Reynales H, López-Medina E, Borja-Tabora C, et al. Three-year Efficacy and Safety of Takeda’s Dengue Vaccine Candidate (TAK-003). Clinical Infectious Diseases. 2022 Jul 1;75(1):107–17.
23. Marangoni D, Barbiero A, Spinicci M, Bartoloni A, Rossanese A, Bonanni P, et al. State of the Art on Vaccine Development Against Dengue Infection: Scoping Review of the Literature. Infect Dis Rep. 2025 Sep 17;17(5):117.
24. Foucambert P, Esbrand FD, Zafar S, Panthangi V, Cyril Kurupp AR, Raju A, et al. Efficacy of Dengue Vaccines in the Prevention of Severe Dengue in Children: A Systematic Review. Cureus. 2022 Sep 8;
25. Patel SS, Rauscher M, Kudela M, Pang H. Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate. Clinical Infectious Diseases. 2023 Feb 1;76(3):E1350–9.
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