Please use this identifier to cite or link to this item:
|Title:||Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity||Authors:||Bidet, K.
Florez de Sessions, P.
|Issue Date:||2019||Publisher:||Nature Publishing Group||Citation:||Bidet, K., Ho, V., Chu, C.W., Naim, A.N.H., Thazin, K., Chan, K.R., Low, J.G.H., Choy, M.M., Wong, L.H., Florez de Sessions, P., Lee, Y.H., Hibberd, M.L., Ooi, E.E., Fink, K., Chen, J. (2019). Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity. npj Vaccines 4 (1) : 3. ScholarBank@NUS Repository. https://doi.org/10.1038/s41541-019-0119-3||Rights:||Attribution 4.0 International||Abstract:||Neutralizing antibodies (nAbs) are a critical component for protection against dengue virus (DENV) infection, but little is known about the immune mechanisms governing their induction and whether such mechanisms can be harnessed for vaccine development. In this study, we profiled the early immune responses to flaviviruses in human peripheral blood mononuclear cells and screened a panel of toll-like receptor (TLR) agonists that stimulate the same immune signatures. Monocyte/macrophage-driven inflammatory responses and interferon responses were characteristics of flavivirus infection and associated with induction of nAbs in humans immunized with the yellow fever vaccine YF-17D. The signatures were best reproduced by the combination of TLR agonists Pam3CSK4 and PolyI:C (PP). Immunization of both mice and macaques with a poorly immunogenic recombinant DENV-2 envelope domain III (EDIII) induced more consistent nAb and CD4+ T-cell responses with PP compared to alum plus monophosphoryl lipid A. Induction of nAbs by PP required interferon-mediated signals in macrophages in mice. However, EDIII + PP vaccination only provided partial protection against viral challenge. These results provide insights into mechanisms underlying nAb induction and a basis for further improving antigen/adjuvant combinations for dengue vaccine development. © 2019, The Author(s).||Source Title:||npj Vaccines||URI:||https://scholarbank.nus.edu.sg/handle/10635/212771||ISSN:||20590105||DOI:||10.1038/s41541-019-0119-3||Rights:||Attribution 4.0 International|
|Appears in Collections:||Elements|
Show full item record
Files in This Item:
|10_1038_s41541-019-0119-3.pdf||3.67 MB||Adobe PDF|
checked on Oct 1, 2022
checked on Sep 29, 2022
This item is licensed under a Creative Commons License