Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: results of a Phase I randomized trial.
The development of a safe and effective malaria vaccine is impeded by the complexity of the Plasmodium life cycle. A vaccine that elicits both cell-mediated and humoral immune responses might be needed for protection against this multistage parasitic infection. Apical membrane antigen 1 (AMA-1) plays a key role in erythrocytic invasion but is also expressed in sporozoites and in late stage liver schizonts, where it may provide a target of protective cell-mediated immunity (CMI). A Phase 1 trial of a vaccine consisting of recombinant AMA-1 protein and the Adjuvant system AS02A was conducted in 60 Malian adults aged 18-55 years who were randomized to receive either half-dose (25 microg/0.25 ml) or full dose (50 microg/0.5 ml) FMP2.1/AS02A or a control rabies vaccine. Interleukin 5 (IL-5) and interferon-gamma (IFN-gamma) production as evaluated by ELISpot and lymphocyte proliferation were measured after in vitro AMA-1 stimulation of peripheral blood mononuclear cells (PBMCs) collected on Days 0 and 90. Post-FMP2.1/AS02A immunization mean stimulation indices were significantly elevated as were the number of IL-5 spot forming cells (SFC)/10(6) PBMC, but no difference was noted in INF-gamma production between the AMA-1/AS02A vaccinated group and the rabies group. These results provide evidence that complex immune responses can be induced by this vaccination strategy and add further impetus for the continuing clinical evaluation of this vaccine.
Lyke
Kirsten E
KE
Center for Vaccine Development, University of Maryland, Baltimore, MD, United States. KLyke@medicine.umaryland.edu
Daou
Modibo
M
Diarra
Issa
I
Kone
Abdoulaye
A
Kouriba
Bourema
B
Thera
Mohamadou A
MA
Dutta
Sheetij
S
Lanar
David E
DE
Heppner
D Gray
DG
Doumbo
Ogobara K
OK
Plowe
Christopher V
CV
Sztein
Marcelo B
MB
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004311:Double-Blind Method; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008565:Membrane Proteins / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D015848:Interleukin-5; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D007371:Interferon-gamma