The Role of Pre-existing Cross-Reactive Central Memory CD4 T-Cells in Vaccination With Previously Unseen Influenza Strains

• Main Authors: 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
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-04-01
• Series: Frontiers in Immunology
• Subjects: influenza vaccination; vaccination efficacy; pre-existing cross-reactive T-cells; central memory T-cell; clonotype diversity
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2019.00593/full

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 pre-existing 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 pre-existing cross-reactive cellular memory might help to improve vaccination outcome.