Abstract
Clinical immunity to malaria is associated with the acquisition of IgG specific for members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens on the surface of infected erythrocytes (IEs). The VAR2CSA subtype of PfEMP1 mediates IE binding in the placenta. VAR2CSA-specific IgG is normally acquired only after exposure to placental parasites. However, it was recently reported that men and children from Colombia often have high levels of functional VAR2CSA-specific IgG. This potentially undermines the current understanding of malaria immunity in pregnant women, and we thus conducted a study to assess further the levels of VAR2CSA-specific IgG in pregnant and nonpregnant Colombians. Plasma IgG against two full-length recombinant PfEMP1 proteins (one of the VAR2CSA type and one not) produced in baculovirus-transfected insect cells was detected frequently among Colombian men, children, and pregnant women with acute or previous malaria exposure. In contrast, IgG reactivity to a homologous full-length VAR2CSA-type protein expressed in Chinese hamster ovary (CHO) cells was low and infrequent among the Colombian plasma samples, as was reactivity to both corresponding native PfEMP1 proteins. Moreover, human and rabbit antibodies specific for Plasmodium vivax Duffy-binding protein (PvDBP), a protein with some homology to PfEMP1, did not react with VAR2CSA-type recombinant or native proteins, although the mouse monoclonal and PvDBP-specific antibody 3D10 was weakly reactive with recombinant proteins expressed in baculovirus-transfected insect cells. Our data indicate that the previously reported Colombian IgG reactivity to recombinant VAR2CSA is not malaria specific and that the acquisition of VAR2CSA-specific IgG is restricted to pregnancy, in Colombia and elsewhere.
Highlights
Clinical immunity to malaria is associated with the acquisition of IgG specific for members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens on the surface of infected erythrocytes (IEs)
Significant plasma levels of IgG specific for VAR2CSA-type PfEMP1 are usually restricted to P. falciparum-exposed women who are or have recently been pregnant, and the levels generally correlate with parity among such women [18, 19]
Gnidehou et al recently reported that this does not appear to be the case in Colombia, as antibodies to recombinant VAR2CSA proteins did not depend on parity and were prevalent among malaria-exposed women, men, and children [16]
Summary
Clinical immunity to malaria is associated with the acquisition of IgG specific for members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of clonally variant antigens on the surface of infected erythrocytes (IEs). For the first time, they become highly susceptible to malaria, despite any clinical immunity acquired earlier in life [5] This appears related to the ability of P. falciparum parasites to express a particular PfEMP1 subtype called VAR2CSA, which is antigenically distinct from all other PfEMP1 proteins and facilitates the selective accumulation of IEs in the placenta [6, 7]. At least 1 million women of reproductive age live in areas of the country where malaria is endemic, malaria in pregnancy, including placental malaria, is uncommon [13,14,15] It was highly surprising when Gnidehou et al reported a high prevalence of VAR2CSA-specific IgG in Colombia, in women with a history of pregnancy and among nulligravidae, men, and children living in areas of the country where malaria is endemic [16]. That same group recently proposed that the high VAR2CSA reactivity among Colombians might be related to cross-reactive antibodies induced by the P. vivax Duffy-binding protein (PvDBP) [17], which has low-level homology to PfEMP1
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