Author:
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França, Camila T.; Li Wai Suen, Connie S. N.; Carmagnac, Amandine; Lin, Enmoore; Kiniboro, Benson; Siba, Peter; Schofield, Louis; Mueller, Ivo
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Abstract:
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BACKGROUND: Further reduction in malaria prevalence and its
eventual elimination would be greatly facilitated by the
development of biomarkers of exposure and/or acquired immunity
to malaria, as well as the deployment of effective vaccines
against Plasmodium falciparum and Plasmodium vivax. A better
understanding of the acquisition of immunity in
naturally-exposed populations is essential for the
identification of antigens useful as biomarkers, as well as to
inform rational vaccine development. METHODS: ELISA was used to
measure total IgG to a synthetic form of
glycosylphosphatidylinositol from P. falciparum (PfGPI) in a
cohort of 1-3 years old Papua New Guinea children with
well-characterized individual differences in exposure to P.
falciparum and P. vivax blood-stage infections. The relationship
between IgG levels to PfGPI and measures of recent and past
exposure to P. falciparum and P. vivax infections was
investigated, as well as the association between antibody levels
and prospective risk of clinical malaria over 16 months of
follow-up. RESULTS: Total IgG levels to PfGPI were low in the
young children tested. Antibody levels were higher in the
presence of P. falciparum or P. vivax infections, but
short-lived. High IgG levels were associated with higher risk of
P. falciparum malaria (IRR 1.33-1.66, P = 0.008-0.027),
suggesting that they are biomarkers of increased exposure to P.
falciparum infections. Given the cross-reactive nature of
antibodies to PfGPI, high IgG levels were also associated with
reduced risk of P. vivax malaria (IRR 0.65-0.67, P =
0.039-0.044), indicating that these antibodies are also markers
of acquired immunity to P. vivax. CONCLUSIONS: This study
highlights that in young children, IgG to PfGPI might be a
useful marker of immune-status to both P. falciparum and P.
vivax infections, and potentially useful to help malaria control
programs to identify populations at-risk. Further functional
studies are necessary to confirm the potential of PfGPI as a
target for vaccine development. |