DENGUE continues to pose a significant public health threat in many parts of the world, so the development of an effective vaccine remains a priority. TAK-003, a live-attenuated tetravalent dengue vaccine has now become a promising candidate for prevention of dengue, as a Phase II clinical trial demonstrated encouraging data on its ability to stimulate cellular immunity, a crucial component of protection against dengue infection. The study, involving 200 participants aged 4-16 years, administered TAK-003 in a two-dose regimen on Days 1 and 90, in children and adolescents living in dengue-endemic countries. TAK-003 elicited robust and durable T cell responses, as shown by the use of interferon-gamma (IFN-γ) enzyme-linked immunospot assay (ELISPOT) and intracellular cytokine staining.
Key findings demonstrated high T cell response rates, as one month after the second dose, 97.1% of participants showed T cell responses against any dengue virus (DENV) peptide pool, with similar rates in both dengue-seropositive (96.0%) and seronegative (98.6%) individuals at baseline. The vaccine also demonstrated broad serotype coverage with T cell responses against all four DENV serotypes, with rates of 79.8%, 90.2%, 77.3%, and 74.0% for DENV-1, -2, -3, and -4, respectively. T cell responses remained elevated for up to 3 years post-vaccination, indicating the potential for long-lasting protection. Both CD4 and CD8 T cells demonstrated multifunctionality, with CD8 T cells typically secreting IFN-γ and TNF-α, and CD4 T cells producing combinations of IFN-γ, IL-2, and TNF-α. Neutralising antibody titres and seropositivity rates remained substantially elevated throughout the 3-year follow-up period and TAK-003 was well-tolerated by the study participants.
The findings have significant implications for dengue prevention strategies in endemic areas. The vaccine’s ability to elicit strong T cell responses against all four DENV serotypes and its efficacy in both seropositive and seronegative individuals, suggests it could be a valuable tool in comprehensive dengue control programmes. While these are promising results, larger Phase IIV trials are necessary for confirming the vaccine’s efficacy and safety profile in broader populations and long-term follow-up studies will be crucial in helping determine the duration of protection and any potential need for booster doses.
Reference
Mandaric et al. Long term T cell response and safety of a tetravalent dengue vaccine in healthy children. Vaccines. 2024;9(1):192.
