Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes.

Abstract

SummaryIgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falcipamm-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytec development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibodydependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations.

Antigenic Diversity of Plasmodium falciparum and Antibody‐Mediated Parasite Neutralization

“…Using IgG from the sera of African adults immune to malaria for passive immunization of P. falciparum-infected nonimmune Thai patients, Bouharoun-Tayoun et al [3] demonstrated a reproducible clinical and parasitological improvement. In vitro, the clinically effective IgG had no detectable inhibitory effect on either parasite invasion or growth, but in some instances it rather enhanced parasite growth [3]. In contrast, the IgG-inhibited parasite growth ef®ciently in co-operation with normal human monocytes in an antibody-dependent cellular inhibition (ADCI) assay.…”

“…Antibodies may mediate protection against infection with asexual blood stages of P. falciparum, as demonstrated by passive transfer experiments with immunoglobulin (Ig)G from adult Africans to Gambian children [2] or to adult Thai patients [3]. However, the target antigens in this context were not de®ned, but merozoite surface antigens, antigens present in the apical organelles of merozoites and antigens expressed on the surface of infected erythrocytes are the most likely candidates [4,5].…”

Identification of frequently recognized dimorphic T-cell epitopes in plasmodium falciparum merozoite surface protein-1 in West and East Africans: lack of correlation of immune recognition and allelic prevalence.

“…38,39 However, IFN-␥ does not control parasite growth by direct elimination of intra-erythrocytic parasites. [40][41][42] In the present study, frequently recognized T-cell epitopes of MSP1 distributed throughout the protein were identified in naturally exposed malaria adults in The Gambia. The level of IFN-␥ reactivity (Ͼ 80%) to MSP1 epitopes was considerably higher than in previous proliferative studies of this antigen (range 30% to 40%) in naturally exposed West African donors.…”

Cross-reactive anti-PfCLAG9 antibodies in the sera of asymptomatic parasite carriers of Plasmodium vivax

“…Existence of regulatory interactions between parasites in mixed infections has been previously also suggested by Bouharoun-Tayoun et al (1990). In their experiments, passive transfer of IgG collected from adult immune donors to P. falciparum malaria infections, from West Africa, to young Thai patient receivers, with active P. falciparum infections, resulted in a significant decrease of the P. falciparum parasitaemia and improvement of clinical symptoms.…”