Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination

Katharina Wild,Bertram Bengsch,Martin Schwemmle,Robert Thimme,Katharina Zoldan,Tobias Boettler,Maike Smits,Maike Hofmann,Florian Krammer,Christoph Neumann-Haefelin,Shirin Strohmeier,Saskia Killmer

doi:10.1038/s41467-021-27064-3

Abstract

Effectiveness of seasonal influenza vaccination varies between individuals and might be affected by vaccination history among other factors. Here we show, by monitoring frequencies of CD4 T cells specific to the conserved hemagglutinin epitope HA118-132 and titres of IgG against the corresponding recombinant hemagglutinin protein, that antigen-specific CD4 T cell and antibody responses are closely linked to pre-existing immunity and vaccine history. Upon immunization, a strong early reaction is observed in all vaccine naïve participants and also in vaccine experienced individuals who have not received the respective seasonal vaccine in the previous year. This response is characterized by HA118-132 specific CD4 T cells with a follicular helper T cell phenotype and by ascending titers of hemagglutinin-specific antibodies from baseline to day 28 following vaccination. This trend was observed in only a proportion of those participants who received the seasonal vaccine the year preceding the study. Regardless of history, levels of pre-existing antibodies and CD127 expression on CD4 T cells at baseline were the strongest predictors of robust early response. Thus, both pre-existing immunity and vaccine history contribute to the response to seasonal influenza vaccines.

Highlights

Effectiveness of seasonal influenza vaccination varies between individuals and might be affected by vaccination history among other factors
Since germinal center (GC)-derived T follicular helper (Tfh) cells are difficult to assess in humans, circulating Tfh cells are commonly used as surrogates as they share phenotypic, functional, and clonal characteristics with lymphoid tissue-derived GC-Tfh cells[16,17,18,19,20,21]
In order to longitudinally analyze circulating influenza-specific CD4 T cells responding to the vaccine (Fig. 1a), we focused on two HLA-DRB1*01:01–major histocompatibility complex (MHC) class-II-restricted HA3-derived epitopes (HA118-132 VPDYASLRSLVASSG and HA306-318 PKYVKQNTLKLAT) in 12 individuals (Table 1)

Summary

Introduction

Effectiveness of seasonal influenza vaccination varies between individuals and might be affected by vaccination history among other factors. A strong early reaction is observed in all vaccine naïve participants and in vaccine experienced individuals who have not received the respective seasonal vaccine in the previous year This response is characterized by HA118-132 specific CD4 T cells with a follicular helper T cell phenotype and by ascending titers of hemagglutininspecific antibodies from baseline to day 28 following vaccination. This trend was observed in only a proportion of those participants who received the seasonal vaccine the year preceding the study. Activation patterns of vaccine-induced, influenza-specific CD4 T cell responses correlate with vaccine-elicited antibody titers and baseline factors that might be able to predict the cellular and humoral response to the vaccine are observed

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