Plasmodium falciparum: A major role for IgG3 in antibody-dependent monocyte-mediated cellular inhibition of parasite growth in vitro

In an attempt to identify parasite antigen-specific antibody isotype(s) med iating inhibition of growth in wine, we tested unfractionated sera and thei r corresponding purified antibody isotype-containing fractions in in vitro assays with asexual-stage parasites of Plasmodium falciparum in the presenc e or absence of monocytes. Using affinity purification techniques, we fract ionated individual and pooled serum samples from semi-immune Gabonese adult s, to obtain samples containing either IgG1, 2. 3, and 4, IgG1, 2, and 4, o r IgG3 alone, and a non-IgG fraction. Antibodies were quantified spectropho tometrically and the presence of different isotypes in individual fractions was confirmed by protein gel electrophoresis. In the absence of monocytes, we observed inhibition of parasite growth with whole serum and varying lev els of either growth enhancement or inhibition with purified Ig-containing fractions. When used in a standardized assay of antibody-dependent cellular inhibition (ADCI) with a monocyte:infected erythrocyte ratio of 1:1, seven of eight serum samples Inhibited growth to a mean level of 42%, and the di fferent Ig-containing fractions displayed varying mean levels of inhibition : IgG3, 44%; IgG;1-4, 22%; IgG1, 2, and 4, 10%; and non-IgG, -10%. The resu lts suggest that, among the different isotypes present in the serum of semi -immune individuals, parasite antigen-specific IgG3 in particular may play an important role in controlling parasitemia via an ADCI mechanism involvin g monocyte-derived mediators, (C) 2001 Academic Press.