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Santos-Peral, A.* ; Luppa, F.* ; Goresch, S.* ; Nikolova, E.* ; Zaucha, M.* ; Lehmann, L.* ; Dahlstroem, F.* ; Karimzadeh, H.* ; Thorn-Seshold, J.* ; Winheim, E.* ; Schuster, E.M.* ; Dobler, G.* ; Hoelscher, M.* ; Kümmerer, B.M.* ; Endres, S. ; Schober, K.* ; Krug, A.B.* ; Pritsch, M.* ; Barba-Spaeth, G.* ; Rothenfußer, S.

Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection.

Nat. Commun. 15:1696 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
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The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Borne Encephalitis-virus; Fusion-loop; Dependent Enhancement; Structural Basis; Igg Antibodies; Immunization; Recognition; Cells; Assay
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 1696 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-522100-001
Grants Projekt DEAL
DOI 10.1038/s41467-024-45806-x
WOS ID 001177163800026
Scopus ID 85185917073
PubMed ID 38402207
Erfassungsdatum 2024-04-24
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