title: Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum.
abstract: We compared the safety and immunogenicity of the recombinant Plasmodium falciparum MSP1(42) antigen formulated with four novel adjuvant systems (AS01B, AS02A, AS05 and AS08) to alum in rhesus monkeys. All five formulations of MSP1(42) were safe and immunogenic. Whereas, all MSP1(42) formulations tested generated high stimulation indices for lymphocyte proliferation (ranging from 27 to 50), the AS02A and AS01B formulations induced the highest levels of specific anti-MSP1(42) antibody. ELISPOT assays showed that the AS02A and AS01B vaccine formulations-induced different cytokine response profiles. Using the ratio of IFN-gamma/IL-5 secreting cells as the metric, the AS01B formulation induced a strong Th1 response, whereas the AS02A formulation induced a balanced Th1/Th2 response. The IFN-gamma response generated by AS02A and AS01B formulations persisted at least 24 weeks after final vaccination. The notable difference in Th1/Th2 polarization induced by the AS02A and AS01B formulations warrants comparative clinical testing.
authors.affiliation: Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand. SathitP@AFRIMS.ORG
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.forename: R Scott
authors.initials: RS
authors.lastname: Miller
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lyon
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Pongsri
authors.initials: P
authors.lastname: Tongtawe
authors.forename: David L
authors.initials: DL
authors.lastname: Ruble
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Joe D
authors.initials: JD
authors.lastname: Cohen
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Walsh
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D015703:Antigens, CD / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000276:immunology* / Q000633:toxicity; D020066:Merozoite Surface Protein 1 / Q000009:adverse effects / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000913:Antibodies, Protozoan; D015703:Antigens, CD; D019013:CD40 Antigens; D016207:Cytokines; D015848:Interleukin-5; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D014614:Vaccines, Synthetic; C041524:aluminum sulfate; D007371:Interferon-gamma; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1