PLASMODIUM-FALCIPARUM - SELECTION OF PARASITE SUBPOPULATIONS WITH DECREASED SENSITIVITY FOR ANTIBODY-MEDIATED GROWTH-INHIBITION IN-VITRO

The chronic, recrudescent nature of malaria has been linked to antigen ic diversity of the parasite in which protective immunity against Plas modium falciparum may be obtained after repeated exposure to infection during a long time. In this study we show that parasite populations w ith decreased sensitivity to antibody-mediated growth inhibition are r eadily generated in vitro. A laboratory strain, F32, was cultured for long periods (10-12 weeks) in the presence of suboptimal inhibitory an tibody concentrations. The antibodies used were the human monoclonal a ntibody 33G2 reacting with a linear epitope of the P. falciparum blood -stage antigen 332 and rabbit antibodies to repeat sequences of the bl ood-stage antigen Pf155/RESA. Our data indicate that the P. falciparum parasites adapt to antibody pressure as reflected by their specifical ly decreased sensitivity to growth inhibition. A relative resistance o f the parasite to growth inhibition mediated by the antibodies used in the culture developed successively, while the parasite remained sensi tive to growth inhibition by other antibodies. When the antibody press ure was removed a successive return of sensitivity to growth inhibitio n developed. Immunofluorescence did not reveal any significant differe nce in antigen expression between the parasite populations. However, P CR analysis showed that a new population appeared in the parasites gro wn in the presence of mAb 33G2, while no such change was detected in t hose grown in the presence of the rabbit antibodies. Our data suggest that the specific decrease in sensitivity to growth inhibition may eit her be due to down-regulation of antigen synthesis or expression by an tibody pressure or, that antibody pressure selects for parasites with low expression of a specific antigen from a heterogeneous parasite pop ulation.