Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum.
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.
Pichyangkul
Sathit
S
Department of Immunology and Medicine, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand. SathitP@AFRIMS.ORG
Gettayacamin
Montip
M
Miller
R Scott
RS
Lyon
Jeffrey A
JA
Angov
Evelina
E
Tongtawe
Pongsri
P
Ruble
David L
DL
Heppner
D Gray
DG
Kester
Kent E
KE
Ballou
W Ripley
WR
Diggs
Carter L
CL
Voss
Gerald
G
Cohen
Joe D
JD
Walsh
Douglas S
DS
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
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