Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine

J Immunol. 2012 May 15;188(10):5054-62. doi: 10.4049/jimmunol.1102710. Epub 2012 Apr 13.


RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials. We report an analysis of cellular immune response to component Ags of RTS,S-hepatitis B surface Ag (HBs) and P. falciparum circumsporozoite (CS) protein-among Tanzanian children in a phase IIb RTS,S/AS01(E) trial. RTS,S/AS01 (E) vaccinees make stronger T cell IFN-γ, CD69, and CD25 responses to HBs peptides than do controls, indicating that RTS,S boosts pre-existing HBs responses. T cell CD69 and CD25 responses to CS and CS-specific secreted IL-2 were augmented by RTS,S vaccination. Importantly, more than 50% of peptide-induced IFN-γ(+) lymphocytes were NK cells, and the magnitude of the NK cell CD69 response to HBs peptides correlated with secreted IL-2 concentration. CD69 and CD25 expression and IL-2 secretion may represent sensitive markers of RTS,S-induced, CS-specific T cells. The potential for T cell-derived IL-2 to augment NK cell activation in RTS,S-vaccinated individuals, and the relevance of this for protection, needs to be explored further.

Trial registration: NCT00380393.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cells, Cultured
  • Epitopes / immunology*
  • Humans
  • Infant
  • Interleukin-2 / metabolism*
  • Kenya
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / parasitology
  • Lymphocyte Activation / immunology
  • Malaria Vaccines / administration & dosage*
  • Malaria Vaccines / immunology
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / administration & dosage
  • Protozoan Proteins / immunology
  • Protozoan Proteins / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / parasitology
  • Tanzania


  • Biomarkers
  • Epitopes
  • Interleukin-2
  • Malaria Vaccines
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan

Associated data