Highly Sensitive Flow Cytometry Allows Monitoring of Changes in Circulating Immune Cells in Blood After Tdap Booster Vaccination

• Published in: Frontiers in Immunology
• Main Authors: Diks, Annieck M., Khatri, Indu, Oosten, Liesbeth E.M., Mooij, Bas de, Groenland, R. J., Teodosio, Cristina, Pérez-Andrés, Martin, Orfao, Alberto, Berbis, G., Jan Zwaginga, Jaap, Dongen, J. J. M. van, Berkowska, Magdalena A.
• Other Authors: European Commission, Bill & Melinda Gates Foundation
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: Frontiers Media 2021
• Subjects: Pertussis vaccine; Flow cytometry; Immune monitoring; Plasma cells; Correlation networks; Perez; Groenland
• Online Access: http://hdl.handle.net/10261/261525; https://doi.org/10.3389/fimmu.2021.666953; https://doi.org/10.13039/100000865; https://doi.org/10.13039/501100000780

© 2021 Diks, Khatri, Oosten, de Mooij, Groenland, Teodosio, Perez-Andres, Orfao, Berbers, Zwaginga, van Dongen and Berkowska. Antigen-specific serum immunoglobulin (Ag-specific Ig) levels are broadly used as correlates of protection. However, in several disease and vaccination models these fail to predict immunity. In these models, in-depth knowledge of cellular processes associated with protective versus poor responses may bring added value. We applied high-throughput multicolor flow cytometry to track over-time changes in circulating immune cells in 10 individuals following pertussis booster vaccination (Tdap, Boostrix®, GlaxoSmithKline). Next, we applied correlation network analysis to extensively investigate how changes in individual cell populations correlate with each other and with Ag-specific Ig levels. We further determined the most informative cell subsets and analysis time points for future studies. Expansion and maturation of total IgG1 plasma cells, which peaked at day 7 post-vaccination, was the most prominent cellular change. Although these cells preceded the increase in Ag-specific serum Ig levels, they did not correlate with the increase of Ig levels. In contrast, strong correlation was observed between Ag-specific IgGs and maximum expansion of total IgG1 and IgA1 memory B cells at days 7 to 28. Changes in circulating T cells were limited, implying the need for a more sensitive approach. Early changes in innate immune cells, i.e. expansion of neutrophils, and expansion and maturation of monocytes up to day 5, most likely reflected their responses to local damage and adjuvant. Here we show that simultaneous monitoring of multiple circulating immune subsets in blood by flow cytometry is feasible. B cells seem to be the best candidates for vaccine monitoring. K is supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 707404. The here presented study is a pilot study for the Innovative Medicines Initiative (IMI) ...