Immune signature of acute pharyngitis in a Streptococcus pyogenes human challenge trial

Streptococcus pyogenes causes at least 750 million infections and more than 500,000 deaths each year. No vaccine is currently available for S. pyogenes and the use of human challenge models offer unique and exciting opportunities to interrogate the immune response to infectious diseases. Here, we use high-dimensional flow cytometric analysis and multiplex cytokine and chemokine assays to study serial blood and saliva samples collected during the early immune response in human participants following challenge with S. pyogenes. We find an immune signature of experimental human pharyngitis characterised by: 1) elevation of serum IL-1Ra, IL-6, IFN-γ, IP-10 and IL-18; 2) increases in peripheral blood innate dendritic cell and monocyte populations; 3) reduced circulation of B cells and CD4+ T cell subsets (Th1, Th17, Treg, TFH) during the acute phase; and 4) activation of unconventional T cell subsets, γδTCR + Vδ2+ T cells and MAIT cells. These findings demonstrate that S. pyogenes infection generates a robust early immune response, which may be important for host protection. Together, these data will help advance research to establish correlates of immune protection and focus the evaluation of vaccines.

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March 2021
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All studies must disclose on these points even when the disclosure is negative. No data were excluded Sample testing was not repeated due to availability of samples.
This study was based on comparing participants who did develop pharyngitis after challenge (n=19) with those who did not (n=6) in an initial non-randomised dose-finding human challenge trial to establish a new model of S. pyogenes phayngitis.
During data collection and analysis for this study, the investigators were not blinded. As this study is a follow-up to the previously published primary objective manuscript 'Osowicki, J. et  The axis labels state the marker and fluorochrome used (e.g. CD4-FITC).
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