Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum.
BACKGROUND
The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such 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.


RESULTS
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.


CONCLUSIONS
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
Pombo
David J
DJ
Queensland Institute of Medical Research, Australian Centre for International and Tropical Health and Nutrition, and Cooperative Research Centre for Vaccine Technology, PO Royal Brisbane Hospital, Australia
Lawrence
Gregor
G
Hirunpetcharat
Chakrit
C
Rzepczyk
Christine
C
Bryden
Michelle
M
Cloonan
Nicole
N
Anderson
Karen
K
Mahakunkijcharoen
Yuvadee
Y
Martin
Laura B
LB
Wilson
Danny
D
Elliott
Salenna
S
Elliott
Suzanne
S
Eisen
Damon P
DP
Weinberg
J Brice
JB
Saul
Allan
A
Good
Michael F
MF
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015153:Blotting, Western; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D006801:Humans; D007111:Immunity, Cellular; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000469:parasitology
D000913:Antibodies, Protozoan