Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

Abstract

Many parasitic infections stimulate antibody responses in their mammalian hosts. The ability of these antibodies to protect against disease varies markedly. Research has revealed that functional properties of antibodies determine their role in protection against parasites. Investigations of antibodies against Plasmodium spp. have demonstrated a variety of functional activities, ranging from invasion inhibition and parasite growth inhibition to antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. These activities have been demonstrated with a large variety of parasite molecules at multiple life cycle stages, highlighting the importance of functional antibody responses in malaria. Other parasitic infections have not yet been investigated in similar detail, but these mechanisms are likely to operate in nonmalarial parasitic infections as well. In this report, we review data on the role of functional antibody responses in protection from parasitic infections, highlighting discoveries in malaria, a parasite for which our knowledge base is the most advanced.

Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria

“…Antibody measures towards the IE have traditionally focused on the quantity of bound antibodies and their ability to inhibit IE binding to CSA ( Cutts et al, 2020 ), but there is increasing interest in how antibodies that recognize IE engage with innate immune cells and activate complement ( Aitken et al, 2020 ), which are both determined by biophysical features of the Fab and Fc regions of antibody (reviewed in Arnold and Chung, 2018 ). In recent years, detailed functional and biophysical characterization of antibody responses has led to the identification of specific antibody determinants that correlate with vaccine-induced protection from HIV ( Chung et al, 2015 ), control of latent tuberculosis infection ( Lu et al, 2016 ), transplacental transfer of antibody ( Martinez et al, 2019 ; Jennewein et al, 2019 ), and correlates of vaccine-induced protection in human malaria challenge models ( Suscovich et al, 2020 ).…”

Live Vaccination with Blood-Stage Plasmodium yoelii 17XNL Prevents the Development of Experimental Cerebral Malaria

“…Phagocytes, such as macrophages, engulf parasites and parasitized RBCs, and are required for the final clearance of malaria parasites [ 23 , 26 , 28 , 49 , 50 ]. Many studies have emphasized the role of antibodies in controlling parasitemia, and almost all malaria vaccines aim to induce specific antibodies [ 51 , 52 , 53 ]. Antibodies block the motility and invasion of merozoites and egress from RBCs to exert cytolysis of merozoites through antibody-dependent complement-mediated cytotoxicity [ 54 ], and to enhance phagocytosis [ 55 ].…”

Plasmodium falciparum Malaria Vaccines and Vaccine Adjuvants

“…In malaria infection, antibodies mediate protective immune responses via different mechanisms, such as inhibition of parasite motility, invasion, egress, adhesion and hepatocyte traversal ability, promotion of antibody-dependent complement-mediated sporozoite/merozoite lysis, phagocytosis, antibody-dependent cellular cytotoxicity, transmission-blocking activity, and others [80,106,107] (reviewed in [108]). Interestingly, the generation of natural immunity against P. falciparum is ethnicity dependent.…”

“…The former function discriminates the IgG subclasses into cytophilic (IgG1, IgG3) and non-cytophilic (IgG2, IgG4) antibodies [117][118][119]. The above-mentioned antibody functional properties have been confirmed against the majority of Plasmodium spp., including P. falciparum in different life-cycle stages [108]. Although the role of IgG and its subclasses is significant in host to symptomatic malaria infection, the role of IgM must not be ignored.…”