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Title: Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity
Authors: Bidet, Katell
Ho, Victor
Chu, Collins Wenhan
Ahmad Nazri Mohamed Naim
Thazin, Khaing
Chan, Kuan Rong
Low, Jenny G. H.
Choy, Milly M.
Wong, Lan Hiong
de Sessions, Paola Florez
Lee, Yie Hou
Hibberd, Martin L.
Ooi, Eng Eong
Fink, Katja
Chen, Jianzhu
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Bidet, K., Ho, V., Chu, C. W., Ahmad Nazri Mohamed Naim, Thazin, K., Chan, K. R., . . . Chen, J. (2019). Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity. npj Vaccines, 4(1), 27-. doi:10.1038/s41541-019-0119-3
Journal: npj Vaccines
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.
ISSN: 2059-0105
DOI: 10.1038/s41541-019-0119-3
Schools: School of Biological Sciences 
Organisations: Singapore Immunology Network, A*STAR
Rights: © 2019 The Author(s) (Published in partnership with the Sealy Center for Vaccine Development). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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