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

Vaccine. 2016 May 17;34(23):2546-55. doi: 10.1016/j.vaccine.2016.04.019. Epub 2016 Apr 15.


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.

Keywords: AMA1; FMP2.1/AS02(A); Malaria; Multifunctional; Pediatric; T cell.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cytokines / immunology*
  • Humans
  • Immunization, Secondary
  • Infant
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Interleukin-2 / immunology
  • Malaria Vaccines / therapeutic use*
  • Malaria, Falciparum / prevention & control*
  • Mali
  • Membrane Proteins / immunology*
  • Plasmodium falciparum
  • Protozoan Proteins / immunology*
  • Tumor Necrosis Factor-alpha / immunology


  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Cytokines
  • IFNG protein, human
  • IL17A protein, human
  • IL2 protein, human
  • Interleukin-17
  • Interleukin-2
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • Tumor Necrosis Factor-alpha
  • apical membrane antigen I, Plasmodium
  • Interferon-gamma

Associated data