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

David J. Pombo, Gregor Lawrence, Chakrit Hirunpetcharat, Christine Rzepczyk, Michelle Bryden, Nicole Cloonan, Karen Anderson, Yuvadee Mahakunkijcharoen, Laura B. Martin, Danny Wilson, Salenna Elliott, Suzanne Elliott, Damon P. Eisen, J. Brice Weinberg, Allan Saul, Michael F. Good

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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 γ 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.

LanguageEnglish
Pages610-617
Number of pages8
JournalLancet
Volume360
Issue number9333
DOIs
Publication statusPublished - 24 Aug 2002
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pombo, D. J., Lawrence, G., Hirunpetcharat, C., Rzepczyk, C., Bryden, M., Cloonan, N., ... Good, M. F. (2002). Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet, 360(9333), 610-617. https://doi.org/10.1016/S0140-6736(02)09784-2
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. / Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. In: Lancet. 2002 ; Vol. 360, No. 9333. pp. 610-617.
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Pombo, DJ, Lawrence, G, Hirunpetcharat, C, Rzepczyk, C, Bryden, M, Cloonan, N, Anderson, K, Mahakunkijcharoen, Y, Martin, LB, Wilson, D, Elliott, S, Elliott, S, Eisen, DP, Weinberg, JB, Saul, A & Good, MF 2002, 'Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum', Lancet, vol. 360, no. 9333, pp. 610-617. https://doi.org/10.1016/S0140-6736(02)09784-2

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; Good, Michael F.

In: Lancet, Vol. 360, No. 9333, 24.08.2002, p. 610-617.

Research output: Contribution to journalArticle

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T1 - Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum

AU - Pombo, David J.

AU - Lawrence, Gregor

AU - Hirunpetcharat, Chakrit

AU - Rzepczyk, Christine

AU - Bryden, Michelle

AU - Cloonan, Nicole

AU - Anderson, Karen

AU - Mahakunkijcharoen, Yuvadee

AU - Martin, Laura B.

AU - Wilson, Danny

AU - Elliott, Salenna

AU - Elliott, Suzanne

AU - Eisen, Damon P.

AU - Weinberg, J. Brice

AU - Saul, Allan

AU - Good, Michael F.

PY - 2002/8/24

Y1 - 2002/8/24

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Pombo DJ, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N et al. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet. 2002 Aug 24;360(9333):610-617. https://doi.org/10.1016/S0140-6736(02)09784-2