title: Priming with an adenovirus 35-circumsporozoite protein (CS) vaccine followed by RTS,S/AS01B boosting significantly improves immunogenicity to Plasmodium falciparum CS compared to that with either malaria vaccine alone.
abstract: The RTS,S/AS02A protein-based vaccine consistently demonstrates significant protection against infection with Plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. Here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (Ad35) vector encoding circumsporozoite protein (CS) (Ad35.CS), followed by boosting with RTS,S in an improved MPL- and QS21-based adjuvant formulation, AS01B, maintains antibody responses and dramatically increases levels of T cells producing gamma interferon and other Th1 cytokines in response to CS peptides. The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans.
authors.affiliation: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD, USA. Ann.stewart@na.amedd.army.mil
authors.forename: V Ann
authors.initials: VA
authors.lastname: Stewart
authors.forename: Shannon M
authors.initials: SM
authors.lastname: McGrath
authors.forename: Patrice M
authors.initials: PM
authors.lastname: Dubois
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pau
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Joseph
authors.initials: J
authors.lastname: Shott
authors.forename: Michelle
authors.initials: M
authors.lastname: Cobb
authors.forename: J Robert
authors.initials: JR
authors.lastname: Burge
authors.forename: David
authors.initials: D
authors.lastname: Larson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ware
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitie
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Weverling
authors.forename: Babak
authors.initials: B
authors.lastname: Bayat
authors.forename: Jerome H H V
authors.initials: JH
authors.lastname: Custers
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Dubois
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
mesh_terms: D000256:Adenoviridae / Q000145:classification / Q000235:genetics*; D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D005260:Female; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D053628:Receptors, Thrombopoietin / Q000276:immunology; D012503:Saponins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C493155:RTS,S-AS02A vaccine; D053628:Receptors, Thrombopoietin; D012503:Saponins; C041595:circumsporozoite protein, Protozoan; C082218:MPL protein, human; C078785:saponin QA-21V1; D007371:Interferon-gamma