Long term T cell response and safety of a tetravalent dengue vaccine in healthy children.

Details

Serval ID
serval:BIB_421259B77384
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long term T cell response and safety of a tetravalent dengue vaccine in healthy children.
Journal
NPJ vaccines
Author(s)
Mandaric S., Friberg H., Saez-Llorens X., Borja-Tabora C., Biswal S., Escudero I., Faccin A., Gottardo R., Brose M., Roubinis N., Fladager D., DeAntonio R., Dimero JAL, Montenegro N., Folschweiller N., Currier J.R., Sharma M., Tricou V.
ISSN
2059-0105 (Electronic)
ISSN-L
2059-0105
Publication state
Published
Issued date
17/10/2024
Peer-reviewed
Oui
Volume
9
Number
1
Pages
192
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
As robust cellular responses are important for protection against dengue, this phase 2 study evaluated the kinetics and phenotype of T cell responses induced by TAK-003, a live-attenuated tetravalent dengue vaccine, in 4-16-year-old living in dengue-endemic countries (NCT02948829). Two hundred participants received TAK-003 on Days 1 and 90. Interferon-gamma (IFN-γ) enzyme-linked immunospot assay [ELISPOT] and intracellular cytokine staining were used to analyze T cell response and functionality, using peptide pools representing non-structural (NS) proteins NS3 and NS5 matching DENV-1, -2, -3, and -4 and DENV-2 NS1. One month after the second TAK-003 dose (Day 120), IFN-γ ELISPOT T cell response rates against any peptide pool were 97.1% (95% CI: 93.4% to 99.1%), and similar for baseline dengue seropositive (96.0%) and seronegative (98.6%) participants. IFN-γ ELISPOT T cell response rates at Day 120 were 79.8%, 90.2%, 77.3%, and 74.0%, against DENV-1, -2, -3, and -4, respectively, and remained elevated through 3 years post-vaccination. Multifunctional CD4 and CD8 T cell responses against DENV-2 NS peptides were observed, independent of baseline serostatus: CD8 T cells typically secreted IFN-γ and TNF-α whereas CD4 T cells secreted ≥ 2 of IFN-γ, IL-2 and TNF-α cytokines. NAb titers and seropositivity rates remained substantially elevated through 3 years post-vaccination. Overall, TAK-003 was well tolerated and elicited durable T cell responses against all four DENV serotypes irrespective of baseline serostatus in children and adolescents aged 4-16 years living in dengue-endemic countries. TAK-003-elicited CD4 and CD8 T cells were multifunctional and persisted up to 3 years post-vaccination.
Pubmed
Web of science
Open Access
Yes
Create date
25/10/2024 14:12
Last modification date
31/10/2024 7:13
Usage data