Abstract:
Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific
P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody
responses and the slowly acquired protective immunity probably reflect the clonal antigenic variation and allelic polymorphism
of PfEMP1. However, it is likely that other immune-evasive mechanisms are also involved, such as interference with
formation and maintenance of immunological memory. We measured PfEMP1-specific antibody levels by enzyme-linked immunosorbent
assay (ELISA) and memory B-cell frequencies by enzyme-linked immunosorbent spot (ELISPOT) assay in a cohort of
P. falciparum-exposed nonpregnant Ghanaian women. The antigens used were a VAR2CSA-type PfEMP1 (IT4VAR04) with expression
restricted to parasites infecting the placenta, as well as two commonly recognized PfEMP1 proteins (HB3VAR06 and
IT4VAR60) implicated in rosetting and not pregnancy restricted. This enabled, for the first time, a direct comparison in the same
individuals of immune responses specific for a clinically important parasite antigen expressed only during well-defined periods
(pregnancy) to responses specific for comparable antigens expressed independent of pregnancy. Our data indicate that PfEMP1-
specific B-cell memory is adequately acquired even when antigen exposure is infrequent (e.g., VAR2CSA-type PfEMP1). Furthermore,
immunological memory specific for VAR2CSA-type PfEMP1 can be maintained for many years without antigen reexposure
and after circulating antigen-specific IgG has disappeared. The study provides evidence that natural exposure to P.
falciparum leads to formation of durable B-cell immunity to clinically important PfEMP1 antigens. This has encouraging implications
for current efforts to develop PfEMP1-based vaccines.
