Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

Pombo, David J., Lawrence, Gregor, Hirunpetcharat, Chakrit, Rzepczyk, Christine, Bryden, Michelle, Cloonan, Nicole, Anderson, Karen, Mahakunkijcharoen, Yuvadee, Martin, Laura B., Wilson, Danny, Elliott, Salenna, Elliott, Suzanne, Eisen, Damon P., Weinberg, J. Brice, Saul, Allan and Good, Michael F. (2002) Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. The Lancet, 360 9333: 610-617. doi:10.1016/S0140-6736(02)09784-2

Author Pombo, David J.
Lawrence, Gregor
Hirunpetcharat, Chakrit
Rzepczyk, Christine
Bryden, Michelle
Cloonan, Nicole
Anderson, Karen
Mahakunkijcharoen, Yuvadee
Martin, Laura B.
Wilson, Danny
Elliott, Salenna
Elliott, Suzanne
Eisen, Damon P.
Weinberg, J. Brice
Saul, Allan
Good, Michael F.
Title Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum
Journal name The Lancet   Check publisher's open access policy
ISSN 0140-6736
Publication date 2002-01-01
Sub-type Article (original research)
DOI 10.1016/S0140-6736(02)09784-2
Open Access Status
Volume 360
Issue 9333
Start page 610
End page 617
Total pages 8
Editor R. Horton
D. H. Frankal
Place of publication United Kingdom
Publisher The Lancet Publishing Group
Language eng
Subject C1
321206 Preventive Medicine
730213 Preventive medicine
Abstract Background The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such cell-mediated immunity was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. Methods We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. Findings After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. Interpretation People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine.
Keyword Medicine, General & Internal
Growth In-vitro
Cd4(+) T-cells
Antimicrobial Activity
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Created: Wed, 15 Aug 2007, 04:49:52 EST