Systems Analysis and Controlled Malaria Infection in Europeans and Africans Elucidate Naturally Acquired Immunity

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before and 5 and 11 days after venous inoculation with Plasmodium falciparum sporozoites. We observed differences in immune cell populations, antigen-specific responses and gene expression profiles between Europeans and Africans and among Africans with differing degrees of immunity. Before inoculation, an activated/differentiated state of both innate and adaptive cells, including elevated CD161+CD4+ T cells and interferon-γ production, predicted Africans capable of controlling parasitemia. After inoculation, the rapidity of the transcriptional response and clusters of CD4+ T cells, plasmacytoid dendritic cells and innate T cells were among the features distinguishing Africans capable of controlling parasitemia from susceptible individuals. These findings can guide the development of a vaccine effective in malaria-endemic regions.

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@article{ bib:2021_nature_immunology,
    author = {Sanne E. de Jong and Vincent van Unen and Mikhael D. Manurung and Koen A. Stam and Jelle J. Goeman and Simon P. Jochems and Thomas H{\"o}llt and Nicola Pezzotti and Yoanne D. Mouwenda and Madeleine Eunice Betouke Ongwe and Freia-Raphaella Lorenz and Yvonne C. M. Kruize and Shohreh Azimi and Marion H. K{\"o}nig and Anna Vilanova and Elmar Eisemann and Boudewijn Lelieveldt and Meta Roestenberg and B. Kim Lee Sim and Marcel Reinders and Rolf Fendel and Stephen L. Hoffman and Peter G. Kremsner and Frits Koning and Benjamin Mordm{\"u}ller and Bertrand Lell and Maria Yazdanbakhsh},
    title = { Systems Analysis and Controlled Malaria Infection in Europeans and Africans Elucidate Naturally Acquired Immunity },
    journal = { Nature Immunology },
    year = { 2021 },
    doi = { 10.1038/s41590-021-00911-7 },
}