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.