Differential effect and interaction of monocytes, hyperimmune sera, and immunoglobulin G on the growth of asexual stage Plasmodium falciparum parasites.

Abstract

Abstract. Using a flow cytometry-based parasite growth inhibition assay (GIA) and an antibody-dependent cellular inhibition (ADCI) assay, we have assessed the differential effect and interaction of monocytes, immune sera, and purified immunoglobulins from Kenyan adults on the growth of Plasmodium falciparum parasites in vitro. We found that monocytes from 14 different normal, healthy, non-malaria-exposed donors had varying effects on parasite growth, i.e., inhibition or enhancement of parasitemia, suggesting heterogeneity in anti-parasitic activities of monocytes from individual donors. Twenty-two serum samples collected from clinically immune adults from western Kenya inhibited growth of P. falciparum after 48 hr in culture. In contrast, all IgG preparations, except one, purified from the same serum samples enhanced parasite growth. In ADCI experiments, of the 22 purified IgG samples used, 11 showed ADCI activities with specific growth inhibition (SGI) of more than 10%, with the highest at 27.6%, and the remaining 11 IgG samples had an SGI of less than 10%. Our results also showed that the ratio of IgG1 to IgG3 antibodies, as determined by an indirect immunofluorescence assay, was higher in the high ADCI response group than in the low response group, suggesting that a higher concentration of IgG1 antibodies with a higher IgG1/IgG3 ratio might be associated with ADCI activities. The present study has resulted in the development of simple, reproducible flow cytometry-based GIA and ADCI assays, and also provides baseline information for further investigation of the role of ADCI activity in naturally acquired immune protection against malaria.Development of acquired protective immunity against malaria in human is epidemiologically well documented, but the characteristics of protective immunity are not fully understood. Available immunologic evidence suggests that both humoral and cell-mediated immune responses are essential components of this immunity. 1,2 The development of continuous cultivation of the blood-stage of Plasmodium falciparum by Trager and Jensen 3 provided the basis for the development of the growth inhibition assay (GIA) for assessing the effect of antibodies and other immune factors on parasite invasion and development in erythrocytes. Subsequent in vitro studies revealed that purified IgGs from immune adults resident in malaria-endemic areas inhibit the invasion and development of parasites in vitro. 4,5 This approach has led to the identification of several vaccine candidate antigens from the blood stage of P. falciparum. [6][7][8] Involvement of antibodies in immune protection against P. falciparum blood stages has been established by passive antibody transfer studies in humans. In these studies, several investigators have found that passive transfer of IgGs from immune adults to nonimmune infected children causes a marked decrease in P. falciparum parasitemias 1,9-12 Investigations from the laboratory of Druilhe identified the cooperation of antibodies with monocytes in protection against mala...

Antigenic Diversity of Plasmodium falciparum and Antibody‐Mediated Parasite Neutralization

“…When sera from 22 adults were analyzed for growth inhibition against a laboratory strain of P. falciparum, all sera were inhibitory, although to varying degrees. In contrast, of the total IgG fractions of the sera, only one was inhibitory, while the other 21 IgGs instead enhanced the parasite growth to different degrees [37]. Such enhancement of parasite growth by certain Ig-fractions or malaria sera has also been observed in other studies [31,32], but whether these phenomena are the results of antibody interactions or just re¯ect the growth-promoting effect of the higher protein concentrations provided by the Ig is unclear.…”

“…Sera/Ig from the same area as the parasites showed signi®cantly better inhibition of parasite growth than those from remote areas [33,35]. The inhibitory effects seen with whole sera are, however, not always the result from the action of antibodies, as re¯ected in a study performed in Kenya [37]. When sera from 22 adults were analyzed for growth inhibition against a laboratory strain of P. falciparum, all sera were inhibitory, although to varying degrees.…”

A Novel Antibody-Dependent Cellular Cytotoxicity Mechanism Involved in Defense against Malaria Requires Costimulation of Monocytes FcγRII and FcγRIII

“…Although several groups have confirmed the role of the ADCI mechanism in parasite killing (33)(34)(35), some have reported difficulties in obtaining reproducible results. The design of a technique to cryopreserve validated aliquots from a single cytapheresis and the identification of the conditions necessary to induce ADCI activity by a cloned cell line in a reproducible manner should permit the assay to be performed more easily by other research groups.…”

A biologic basis for integrated malaria control.

“…Immune responses differ between human individuals, due to genetic factors and age as well as particular histories of exposure, and may encompass transmission-blocking effects; aggregates of immune responses differ between human populations, and change with time. 12,13 Interactions between parasites and vectors are highly heterogeneous and dynamic. Complexity suggests that we allow ample margins FIGURE 4.…”