title: Induction of Plasmodium falciparum-specific CD4+ T cells and memory B cells in Gabonese children vaccinated with RTS,S/AS01(E) and RTS,S/AS02(D).
abstract: The recombinant circumsporozoite protein (CS) based vaccine, RTS,S, confers protection against Plasmodium falciparum infection in controlled challenge trials and in field studies. The RTS,S recombinant antigen has been formulated with two adjuvant systems, AS01 and AS02, which have both been shown to induce strong specific antibody responses and CD4 T cell responses in adults. As infants and young children are particularly susceptible to malaria infection and constitute the main target population for a malaria vaccine, we have evaluated the induction of adaptive immune responses in young children living in malaria endemic regions following vaccination with RTS,S/AS01(E) and RTS,S/AS02(D). Our data show that a CS-specific memory B cell response is induced one month after the second and third vaccine dose and that CS-specific antibodies and memory B cells persist up to 12 months after the last vaccine injection. Both formulations also induced low but significant amounts of CS-specific IL-2(+) CD4(+) T cells one month after the second and third vaccine dose, upon short-term in vitro stimulation of whole blood cells with peptides covering the entire CS derived sequence in RTS,S. These results provide evidence that both RTS,S/AS01(E) and RTS,S/AS02(D) induced adaptive immune responses including antibodies, circulating memory B cells and CD4(+) T cells directed against P. falciparum CS protein.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00307021.
authors.affiliation: Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon. agnandjis@yahoo.fr
authors.forename: Selidji T
authors.initials: ST
authors.lastname: Agnandji
authors.forename: Rolf
authors.initials: R
authors.lastname: Fendel
authors.forename: Michaël
authors.initials: M
authors.lastname: Mestré
authors.forename: Michel
authors.initials: M
authors.lastname: Janssens
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
authors.forename: Jana
authors.initials: J
authors.lastname: Held
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Gnansounou
authors.forename: Sonja
authors.initials: S
authors.lastname: Haertle
authors.forename: Isabel
authors.initials: I
authors.lastname: von Glasenapp
authors.forename: Sunny
authors.initials: S
authors.lastname: Oyakhirome
authors.forename: Ludovic
authors.initials: L
authors.lastname: Mewono
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitie
authors.forename: Patrice M
authors.initials: PM
authors.lastname: Dubois
authors.forename: Tonya
authors.initials: T
authors.lastname: Villafana
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.forename: Aurelie
authors.initials: A
authors.lastname: Olivier
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Meral
authors.initials: M
authors.lastname: Esen
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lell
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
mesh_terms: D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000097:blood; D005681:Gabon; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D013045:Species Specificity; D017186:Titrimetry; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533816:RTS,S-AS01E vaccine; C533817:RTS,S-AS02D vaccine; C041595:circumsporozoite protein, Protozoan