Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity
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s41541-019-0119-3.pdf
Description
Published version
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3.58 MB
Format
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Checksum (MD5)
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Author(s)
Bidet, Katell
Ho, Victor
Chu, Collins Wenhan
Naim, Ahmad Nazri Mohamed
Thazin, Khaing
Chan, Kuan Rong
Low, Jenny G. H.
Choy, Milly M.
Wong, Lan Hiong
Florez de Sessions, Paola
Date Issued
June 2019
Journal
NPJ Vaccines
Publisher
Springer Science and Business Media LLC
Citation
Bidet, Katell et al. "Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity." NPJ Vaccines 4, 1 (June 2019): 27 © 2019 The Author(s)
Version
Final published version
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41541-019-0119-3
