A phase 2 study published in Nature has provided comprehensive data on the long-term immunogenicity and safety of TAK-003, a tetravalent dengue vaccine, in healthy children. The open-label study, conducted across sites in Panama and the Philippines, followed participants aged 4-16 years for three years after a two-dose vaccination schedule.
The primary objective was to assess the IFN-γ ELISPOT T cell response one month after the second dose. Secondary objectives included evaluating T cell responses up to 3 years post-vaccination, characterizing T cell phenotypes, and assessing neutralizing antibody (NAb) titers and overall safety. The study design involved administering TAK-003 subcutaneously on days 1 and 90, with blood samples collected at various intervals for immunological assessments.
Sustained T Cell Responses
The study demonstrated that TAK-003 induced sustained T cell responses, as measured by IFN-γ ELISPOT, up to three years after the second dose. A positive T cell response was defined as an IFN-γ ELISPOT response >3 times higher than baseline and ≥5 SFC/106 PBMCs. These findings suggest that TAK-003 can elicit long-term cellular immunity against dengue virus serotypes.
Safety Profile
Safety was a key focus, with adverse events (AEs) monitored throughout the study. The vaccine was generally well-tolerated, with no significant safety concerns identified. Solicited AEs were recorded up to 28 days after each vaccination, while medically attended AEs (MAAEs) were tracked for six months post-second dose. Serious adverse events (SAEs) and febrile episodes were monitored until the study's end date.
Study Design and Methodology
The study enrolled healthy children aged 4-16 years in Panama and 4-8 years in the Philippines. Participants received two doses of TAK-003, administered as a subcutaneous injection into the upper arm on Days 1 and 90. The vaccine formulation contained 3.6 log10 pfu of TDV-1, 4.0 log10 pfu of TDV-2, 4.6 log10 pfu of TDV-3, and 5.1 log10 pfu of TDV-4. Blood samples were taken to assess baseline serostatus and to evaluate T cell responses and NAb titers at various time points.
Implications for Dengue Prevention
Dengue fever is a significant public health concern, with an estimated 390 million infections occurring globally each year. The development of safe and effective vaccines is crucial for preventing dengue and reducing its burden on healthcare systems. This study provides evidence that TAK-003 can induce long-term T cell responses and is generally safe in children, supporting its potential as a valuable tool in dengue prevention strategies. Further research is needed to fully understand the long-term protective efficacy of TAK-003 and its impact on dengue incidence in endemic areas.
