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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in immunology and vaccination

Cellular immune responses induced by immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine.

LSHTM investigators:
Amir Horowitz, Julius Hafalla, Elizabeth King, Denise Dekker, Patrick Corran, Chris Drakeley, Lorenz von Seidlein & Eleanor Riley.
External collaborators:
John Lusingu (National Institute for Medical Research, Tanzania); Amanda Leach, Philippe Moris, Joe Cohen & Johan Vekemans, (GlaxoSmithKline Biologicals, Belgium); Tonya Villafana (PATH Malaria Vaccine Initiative, USA); Philip Bejon (Kenya Medical Research Institute/ Wellcome Trust Programme, Kenya).
Funding body:
PATH Malaria Vaccine Initiative.

RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials.

We conducted an analysis of cellular immune response to   component antigens of RTS,S – hepatitis B surface antigen (HBs) and P. falciparum circumsporozoite (CS) protein – among Tanzanian children in a Phase IIb RTS,S/AS01E trial.  We observed that RTS,S/AS01 E vaccinees make stronger T cell IFN-g, 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-g+ 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.