title: Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines: randomized, double-blind study in malaria-naïve adults.
abstract: This phase II, randomized, double-blind study evaluated the immunogenicity of RTS,S vaccines containing Adjuvant System AS01 or AS02 as compared with non-adjuvanted RTS,S in healthy, malaria-naïve adults (NCT00443131). Thirty-six subjects were randomized (1:1:1) to receive RTS,S/AS01, RTS,S/AS02, or RTS,S/saline at months 0, 1, and 2. Antibody responses to Plasmodium falciparum circumsporozoite (CS) and hepatitis B surface (HBs) antigens were assessed and cell-mediated immune responses evaluated by flow cytometry using intracellular cytokine staining on peripheral blood mononuclear cells. Anti-CS antibody avidity was also characterized. Safety and reactogenicity after each vaccine dose were monitored. One month after the third vaccine dose, RTS,S/AS01 (160.3 EU/mL [95%CI: 114.1-225.4]) and RTS,S/AS02 (77.4 EU/mL (95%CI: 47.3-126.7)) recipients had significantly higher anti-CS antibody geometric mean titers (GMTs) than recipients of RTS,S/saline (12.2 EU/mL (95%CI: 4.8-30.7); P < 0.0001 and P = 0.0011, respectively). The anti-CS antibody GMT was significantly higher with RTS,S/AS01 than with RTS,S/AS02 (P = 0.0135). Anti-CS antibody avidity was in the same range in all groups. CS- and HBs-specific CD4(+) T cell responses were greater for both RTS,S/AS groups than for the RTS,S/saline group. Reactogenicity was in general higher for RTS,S/AS compared with RTS,S/saline. Most grade 3 solicited adverse events (AEs) were of short duration and grade 3 solicited general AEs were infrequent in the 3 groups. No serious adverse events were reported. In conclusion, in comparison with non-adjuvanted RTS,S, both RTS,S/AS vaccines exhibited better CS-specific immune responses. The anti-CS antibody response was significantly higher with RTS,S/AS01 than with RTS,S/AS02. The adjuvanted vaccines had acceptable safety profiles.
authors.affiliation: a Centre for Vaccinology (CEVAC); Ghent University and Ghent University Hospital; Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Isabel
authors.initials: I
authors.lastname: Leroux-Roels
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood; D000915:Antibody Affinity; D016207:Cytokines / Q000032:analysis; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D016207:Cytokines; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C577001:RTS,S-AS01 vaccine; C493155:RTS,S-AS02A vaccine; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan
keywords: AS01; AS02; adjuvant; cell-mediated immunity; humoral immunity; malaria; vaccine