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.
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.
Stewart
V Ann
VA
Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD, USA. Ann.stewart@na.amedd.army.mil
McGrath
Shannon M
SM
Dubois
Patrice M
PM
Pau
Maria G
MG
Mettens
Pascal
P
Shott
Joseph
J
Cobb
Michelle
M
Burge
J Robert
JR
Larson
David
D
Ware
Lisa A
LA
Demoitie
Marie-Ange
MA
Weverling
Gerrit Jan
GJ
Bayat
Babak
B
Custers
Jerome H H V
JH
Dubois
Marie-Claude
MC
Cohen
Joe
J
Goudsmit
Jaap
J
Heppner
D Gray
DG
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
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