Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: Results of a Phase I randomized trial

Center for Vaccine Development, University of Maryland, Baltimore, MD, United States.
Vaccine (Impact Factor: 3.62). 04/2009; 27(15):2171-6. DOI: 10.1016/j.vaccine.2009.01.097
Source: PubMed


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.


Available from: Ogobara K Doumbo
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    • "The same result was observed at the late day 140 time-point. These allele-specific totals are not subject to any double counting error due to peptide homology between the 3D7 and FVO strains, and these median ELISPOT responses compare favourably with those induced by the same vectors and regimen for the ME-TRAP and MSP1 malaria antigens and are substantially greater than those reported for AMA1 protein-in-adjuvant vaccines [44], [45]. Responses induced after the ChAd63 AMA1 immunization also compared favourably with those recently reported following a single immunization of healthy adult US volunteers with 1×1010 vp of an AdHu5 vaccine encoding the 3D7 AMA1 antigen [27], although interestingly in this study the use of a higher dose (5×1010 vp) led to a significant reduction in T cell immunogenicity – an observation not seen here with the same dose of ChAd63. "
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    • "Previous studies have shown that the FMP2.1/AS02A vaccine elicits antibodies that inhibit both parasite growth and AMA1 processing in homologous parasites [16] as well as measurable cellular immune responses [22]. Post-immunization sera from Malian adults who received the 50 µg dose of FMP2.1/AS02A (but not sera from those who received the 25 µg dose) of the malaria vaccine had significantly greater growth inhibition activity against both 3D7 and FVO parasites than did post-immunization sera from the rabies comparator group in the previous Phase 1 trial [17]. "
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    Full-text · Article · Feb 2010 · PLoS ONE
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