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

Santos-Peral A, Luppa F, Goresch S, Nikolova E, Zaucha M, Lehmann L, Dahlstroem F, Karimzadeh H, Thorn-Seshold J, Winheim E, Schuster EM, Dobler G, Hoelscher M, Kümmerer BM, Endres S, Schober K, Krug AB, Pritsch M, Barba-Spaeth G, Rothenfusser S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 15

Article Number: 1696

Journal Issue: 1

DOI: 10.1038/s41467-024-45806-x

Abstract

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.

Authors with CRIS profile

Ev-Marie Schuster Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Kilian Schober Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Klinikum der Universität München DE Germany (DE) Université Sorbonne Paris Cité FR France (FR) Sanitätsakademie der Bundeswehr (SanAkBw) DE Germany (DE) Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE)

How to cite

APA:

Santos-Peral, A., Luppa, F., Goresch, S., Nikolova, E., Zaucha, M., Lehmann, L.,... Rothenfusser, S. (2024). Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection. Nature Communications, 15(1). https://dx.doi.org/10.1038/s41467-024-45806-x

MLA:

Santos-Peral, Antonio, et al. "Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection." Nature Communications 15.1 (2024).

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