The role of pre-existing cross-reactive central memory CD4 T-cells in vaccination with previously unseen influenza strains

Mikalai Nienen, Ulrik Stervbo, Felix Mölder, Sviatlana Kaliszczyk, Leon Kuchenbecker, Ludmila Gayova, Brunhilde Schweiger, Karsten Jürchott, Jochen Hecht, Avidan U. Neumann, Sven Rahmann, Timm Westhoff, Petra Reinke, Andreas Thiel, Nina Babel

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Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains–a process called original antigenic sin. The role of this preexisting cellular immunity in this process is, despite some hints from animal models, not clear. Here, we analyzed cellular and humoral immunity in healthy individuals before and after vaccination with seasonal influenza vaccine. Based on influenza-specific hemagglutination inhibiting (HI) titers, vaccinees were grouped into HI-negative and -positive cohorts followed by in-depth cytometric and TCR repertoire analysis. Both serological groups revealed cross-reactive T-cell memory to the vaccine strains at baseline that gave rise to the majority of vaccine-specific T-cells post vaccination. On the contrary, very limited number of vaccine-specific T-cell clones was recruited from the naive pool. Furthermore, baseline quantity of vaccine-specific central memory helper T-cells and clonotype richness of this population directly correlated with the vaccination efficacy. Our findings suggest that the deliberate recruitment of preexisting cross-reactive cellular memory might help to improve vaccination outcome.

Original languageEnglish
Article number593
JournalFrontiers in Immunology
Issue numberAPR
StatePublished - 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2019 Nienen, Stervbo, Mölder, Kaliszczyk, Kuchenbecker, Gayova, Schweiger, Jürchott, Hecht, Neumann, Rahmann, Westhoff, Reinke, Thiel and Babel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


The project was funded from German Ministry of Education and Research (projects e:KID, Primage), OP EFRE NRW (project Osteosys EFRE-0800427), and the Mercator Research Center Ruhr (project MERCUR Pe-2013-0012). We acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Fund of Charité - Universitätsmedizin Berlin.

FundersFunder number
Universitätsmedizin Berlin
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Charité – Universitätsmedizin Berlin
Mercator Research Center RuhrMERCUR Pe-2013-0012


    • Central memory T-cell
    • Clonotype diversity
    • Influenza vaccination
    • Pre-existing cross-reactive T-cells
    • Vaccination efficacy


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