Clinical Safety Experience of TAK-003 for Dengue Fever: A New Tetravalent Live Attenuated Vaccine Candidate

Clin Infect Dis. 2023 Feb 8;76(3):e1350-e1359. doi: 10.1093/cid/ciac418.


Background: An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals.

Methods: Safety findings are presented herein from an integrated analysis of data for healthy 4-60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender.

Results: The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1-3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively).

Conclusions: No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4-60 years.

Keywords: TAK-003; adverse events; clinical safety; dengue tetravalent vaccine; hospitalization.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral
  • Child
  • Child, Preschool
  • Dengue Vaccines*
  • Dengue*
  • Double-Blind Method
  • Humans
  • Middle Aged
  • Vaccines, Attenuated
  • Young Adult


  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated