title: Plasmodium falciparum-specific cellular immune responses after immunization with the RTS,S/AS02D candidate malaria vaccine in infants living in an area of high endemicity in Mozambique.
abstract: Results from clinical trials in areas where malaria is endemic have shown that immunization with RTS,S/AS02A malaria vaccine candidate induces partial protection in adults and children and cellular effector and memory responses in adults. For the first time in a malaria vaccine trial, we sought to assess the cell-mediated immune responses to RTS,S antigen components in infants under 1 year of age participating in a clinical phase I/IIb trial of RTS,S/AS02D in Mozambique. Circumsporozoite protein (CSP)-specific responses were detected in approximately half of RTS,S-immunized infants and included gamma interferon (IFN-gamma), interleukin-2 (IL-2), and combined IL-2/IL-4 responses. The median stimulation indices of cytokine-producing CD4(+) and CD8(+) cells were very low but significantly higher in RTS,S-immunized infants than in infants that received the comparator vaccine. Protection against subsequent malarial infection tended to be associated with a higher percentage of individuals with CSP-specific IL-2 in the supernatant (P = 0.053) and with higher CSP-specific IFN-gamma-producing CD8(+) T-cell responses (P = 0.07). These results report for the first time the detection of malaria-specific cellular immune responses after vaccination of infants less than 1 year of age and pave the way for future field studies of cellular immunity to malaria vaccine candidates.
authors: Centro de Investigação en Saúde de Manhiça, Manhiça, Mozambique.
authors: Arnoldo
authors: A
authors: Barbosa
authors: Denise
authors: D
authors: Naniche
authors: John J
authors: JJ
authors: Aponte
authors: M Nelia
authors: MN
authors: Manaca
authors: Inacio
authors: I
authors: Mandomando
authors: Pedro
authors: P
authors: Aide
authors: Jahit
authors: J
authors: Sacarlal
authors: Montse
authors: M
authors: Renom
authors: Sarah
authors: S
authors: Lafuente
authors: W Ripley
authors: WR
authors: Ballou
authors: Pedro L
authors: PL
authors: Alonso
mesh_terms: D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D009073:Mozambique; D010919:Placebos / Q000008:administration & dosage; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015800:Protozoan Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D017780:Malaria Vaccines; D010919:Placebos; D015800:Protozoan Proteins; C533817:RTS,S-AS02D vaccine; C041595:circumsporozoite protein, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma