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 cur-
rent understanding of malaria immunity in pregnant women, and we thus con-
ducted 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 reac-
tivity to a homologous full-length VAR2CSA-type protein expressed in Chinese ham-
ster ovary (CHO) cells was low and infrequent among the Colombian plasma sam-
ples, 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
