title: Potent induction of focused Th1-type cellular and humoral immune responses by RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine.
abstract: The RTS,S/SBAS2 vaccine confers sterile protection against Plasmodium falciparum sporozoite challenge. The mechanisms underlying this are of great interest, yet little is known about the immune effector mechanisms induced by this vaccine. The immune responses induced by RTS,S/SBAS2 were characterized in 10 malaria-naive volunteers. Several epitopes in the circumsporozoite protein (CSP) were identified as targets of cultured interferon (IFN)-gamma-secreting CD4+ T cells. RTS,S-specific IFN-gamma-secreting effector T cells were induced in 8 subjects; this ex vivo response mapped to a single peptide in Th2R. CSP-specific CD8+ cytotoxic T lymphocytes were not detected. RTS, S-specific IFN-gamma production was universal, whereas interleukin-4 and -5 production was rare. RTS,S-specific lymphoproliferative responses and antibodies to CSP were strongly induced in all volunteers. Responses waned with time but were boostable. Thus, RTS, S/SBAS2 is a potent inducer of Th1-type cellular and humoral immunity. These results highlight possible immune mechanisms of protection and have important implications for vaccine design in general.
authors.affiliation: Nuffield Dept. of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. ajit.lalvani@ndm. ox.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Lalvani
authors.forename: P
authors.initials: P
authors.lastname: Moris
authors.forename: G
authors.initials: G
authors.lastname: Voss
authors.forename: A A
authors.initials: AA
authors.lastname: Pathan
authors.forename: K E
authors.initials: KE
authors.lastname: Kester
authors.forename: R
authors.initials: R
authors.lastname: Brookes
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
authors.forename: M
authors.initials: M
authors.lastname: Delchambre
authors.forename: K L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: C
authors.initials: C
authors.lastname: Carton
authors.forename: M
authors.initials: M
authors.lastname: Slaoui
authors.forename: C
authors.initials: C
authors.lastname: Van Hoecke
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
authors.forename: J
authors.initials: J
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma