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Merozoite surface protein-3: a malaria protein inducing antibodies that
promote Plasmodium falciparum killing by cooperation with blood monocytes
C Oeuvray, H Bouharoun-Tayoun, H Gras-Masse, E Bottius, T Kaidoh, M Aikawa, MC Filgueira, A Tartar and P Druilhe
Laboratoire de Parasitologie Medicale, Institut Pasteur, Paris, France.
We have previously found that the acquired protection against malaria
implicates a mechanism of defense that relies on the cooperation between
cytophilic antibodies and monocytes. Accordingly, an assay of
antibody-dependent cellular inhibition (ADCI) of parasite growth was used
as a means of selecting for molecules capable of inducing protective
immunity to malaria. This allowed us to identify in the sera of clinically
protected subjects an antibody specificity that promotes parasite killing
mediated by monocytes. This antibody is directed to a novel merozoite
surface protein (MSP-3) of a molecular mass of 48 kD. Purified IgG from
protected subjects are effective in ADCI and those directed against MSP-3
are predominantly cytophilic. In contrast, in nonprotected individuals,
whose antibodies are not effective in ADCI, anti-MSP-3 antibodies are
mostly noncytophilic. A region in MSP-3 targetted by antibodies effective
in the ADCI assay was identified and its sequence was determined; it
contains an epitope not defined by a repetitive structure and does not
appear to be polymorphic. Antibodies raised in mice against a peptide
containing this epitope, as well as human antibodies immunopurified on this
peptide, elicit a strong inhibition of Plasmodium falciparum growth in ADCI
assay, whereas control antibodies, directed to peptides from other
molecules, do not. The correlation between isotypes of antibodies produced
against the 48- kD epitopes, clinical protection, and the ability of
specific anti-MSP- 3 antibodies to block the parasite schizogony in the
ADCI assay suggests that this molecule is involved in eliciting protective
mechanisms.
Volume 84,
Issue 5,
pp. 1594-1602,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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