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Strain-specific Plasmodium falciparum multifunctional CD4+ T cell cytokine expression in Malian children immunized with the FMP2.1/AS02A vaccine candidate

Graves, Shawna F., Kouriba, Bourema, Diarra, Issa, Daou, Modibo, Niangaly, Amadou, Coulibaly, Drissa, Keita, Yamoussa, Laurens, Matthew B., Berry, Andrea A., Vekemans, Johan, Ripley Ballou, W., Lanar, David E., Dutta, Sheetij, Gray Heppner, D., Soisson, Lorraine, Diggs, Carter L., Thera, Mahamadou A., Doumbo, Ogobara K., Plowe, Christopher V., Sztein, Marcelo B., Lyke, Kirsten E.
Vaccine 2016 v.34 no.23 pp. 2546-2555
CD4-positive T-lymphocytes, Plasmodium falciparum, antigens, children, clinical trials, flow cytometry, interferon-gamma, interleukin-17, interleukin-2, malaria, malaria vaccines, parasites, rabies, tumor necrosis factor-alpha
Based on Plasmodium falciparum (Pf) apical membrane antigen 1 (AMA1) from strain 3D7, the malaria vaccine candidate FMP2.1/AS02A showed strain-specific efficacy in a Phase 2 clinical trial in 400 Malian children randomized to 3 doses of the AMA1 vaccine candidate or control rabies vaccine on days 0, 30 and 60. A subset of 10 Pf(−) (i.e., no clinical malaria episodes) AMA1 recipients, 11 Pf(+) (clinical malaria episodes with parasites with 3D7 or Fab9-type AMA1 cluster 1 loop [c1L]) AMA1 recipients, and 10 controls were randomly chosen for analysis. Peripheral blood mononuclear cells (PBMCs) isolated on days 0, 90 and 150 were stimulated with full-length 3D7 AMA1 and c1L from strains 3D7 (c3D7) and Fab9 (cFab9). Production of IFN-γ, TNF-α, IL-2, and/or IL-17A was analyzed by flow cytometry. Among AMA1 recipients, 18/21 evaluable samples stimulated with AMA1 demonstrated increased IFN-γ, TNF-α, and IL-2 derived from CD4+ T cells by day 150 compared to 0/10 in the control group (p<0.0001). Among AMA1 vaccines, CD4+ cells expressing both TNF-α and IL-2 were increased in Pf(−) children compared to Pf(+) children. When PBMCs were stimulated with c3D7 and cFab9 separately, 4/18 AMA1 recipients with an AMA1-specific CD4+ response had a significant response to one or both c1L. This suggests that recognition of the AMA1 antigen is not dependent upon c1L alone. In summary, AMA1-specific T cell responses were notably increased in children immunized with an AMA1-based vaccine candidate. The role of CD4+TNF-α+IL-2+-expressing T cells in vaccine-induced strain-specific protection against clinical malaria requires further exploration. Identifier: NCT00460525.