PuSH - Publication Server of Helmholtz Zentrum München: Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

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

Abstract
Metrics
Extra information

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.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Borne Encephalitis-virus; Fusion-loop; Dependent Enhancement; Structural Basis; Igg Antibodies; Immunization; Recognition; Cells; Assay

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 15, Issue: 1, Article Number: 1696

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)

Grants Projekt DEAL