title: Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine.
abstract: 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.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.
authors.forename: Amir
authors.initials: A
authors.lastname: Horowitz
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Elizabeth
authors.initials: E
authors.lastname: King
authors.forename: John
authors.initials: J
authors.lastname: Lusingu
authors.forename: Denise
authors.initials: D
authors.lastname: Dekker
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Tonya
authors.initials: T
authors.lastname: Villafana
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Corran
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000378:metabolism*; D007630:Kenya; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D013636:Tanzania
chemical_list: D015415:Biomarkers; D000939:Epitopes; D007376:Interleukin-2; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan