At 3 years, the TAK-003 vaccine from Takeda remained effective at protecting against symptomatic dengue fever among children and adolescents. These findings were published in Clinical Infectious Diseases.
Children and adolescents (N=20,071) aged 4 to16 years were recruited from 8 countries for this phase 3, double-blind, placebo-controlled, randomized clinical trial. Participants were randomized in a 2:1 fashion to receive either 2 doses of TAK-003 (n=13,380) or placebo (n=6687) at months 0 and 3. Efficacy and safety were evaluated over a period of 4 to4.5 years, and a subset of 4000 participants were assessed for immunogenicity.
A total of 23,693 participants reported febrile illness and 895 had a confirmed diagnosis of dengue fever. Among participants with confirmed dengue fever, all 4 serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) were identified among those in Asia and serotypes DENV-1 and DENV-2 were observed among only those in Latin America.
After stratification by serotype, the researchers found that the hospitalization rates were 41.9%, 17.6%, 16.3%, and 14.4% among participants who received DENV-2, DENV-4, and DENV-1, respectively. Stratified by study site, hospitalization rates were 68.0% for Sri Lanka, 37.7% for Thailand, 200% for Nicaragua, 18.2% for Dominican Republic, 15.4% for Colombia, 9.4% for Philippines, 9.1% for Brazil, and 2.5% for Panama.
The cumulative efficacy of the TAK-003 was 62.0% (95% CI, 56.6-66.7) for protection against dengue fever and 83.6% (95% CI, 76.8-88.4) for decreasing the risk for hospitalization. Stratified by serotypes, the efficacy of the TAK-003 vaccine ranged between 52.3% (DENV-3) and 83.4% (DENV-2).
At the 3-year follow-up, the efficacy of the vaccine had decreased to 44.7% for protection against dengue fever (95% CI, 32.5-54.7) and the risk for hospitalization had decreased to 70.8% (95% CI, 49.6-83.0). Stratified by serotype, the efficacy vaccine ranged between 15.2% (DENV-3) and 72.1% (DENV-2).
Geometric mean titer values remained similar through month 27 among all study participants. Tetravalent seropositivity was observed among 80.5% of participants who received the vaccine and had been seropositive for dengue fever at baseline and 98.4% of those who were seronegative at baseline.
Adverse events occurred among 2.9% of participants who received the TAK-003 vaccine and 3.5% of those who received placebo. Severe adverse events occurred among less than 1% of participants in each group. In addition, none of the severe adverse events were related to the TAK-003 vaccine or the study protocol. A total of 7 participants, of whom 5 had received the TAK-003 vaccine and 2 had received placebo, died during the study; however, no deaths were attributed to the TAK-003 vaccine.
This study was limited by its small population of participants with DENV-4 infection. In addition, most cases of DENV-4 infection occurred toward the end of the study period, which may indicate waning protection from the vaccine against this serotype.
The researchers concluded that the TAK-003 vaccine effectively protected children and adolescents against dengue fever and was associated with a decreased the risk for hospitalization. However, trends varied across regions and by serotypes, with evidence suggesting that the efficacy of the vaccine declines over time. This study is ongoing and there are plans to assess the efficacy of a booster vaccine.
Disclosure: Some author(s) declared affiliations with industry. Please see the original reference for a full list of disclosures.
Rivera L, Biswal S, Sáez-Llorens X, et al. Three years efficacy and safety of Takeda’s dengue vaccine candidate (TAK-003). Clin Infect Dis. 2021;ciab864. doi:10.1093/cid/ciab864