IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children

Abstract

BackgroundFurther 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.MethodsELISA 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.ResultsTotal 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-2042-2) contains supplementary material, which is available to authorized users.

Antigenicity and immune correlate assessment of seven Plasmodium falciparum antigens in a longitudinal infant cohort from northern Ghana

“…The observations collectively suggest that the measured antibodies are potential markers of the extent of exposure to infectious bites, and this has previously been described for both pre-erythrocytic and erythrocytic stage parasites in this age group of children 12,28,29 . Antibodies in this age group appear to be markers of exposure rather than correlates of protection because their levels are probably below the threshold required to achieve clinical immunity 8,12,30,31 .…”

Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria

“…Consistent with the property of GPI in inducing malaria-like symptoms, immunization of mice with a synthetic glycan portion of GPI produced anti-GPI antibodies, and immunized mice infected with P. berghei ANKA, an experimental cerebral malaria model, were protected from cerebral malaria (98). Further, the presence of anti-GPI antibodies in people in malaria endemic was associated with a significant protective immunity against malaria illnesses (99, 100).…”

Unveiling the Sugary Secrets of Plasmodium Parasites

“…In contrast, Abs from children with severe symptoms did not recognize truncated GPIs but showed a stronger response against the full structure (Tamborrini et al, 2010). Confirming these observations, high IgG titers against Plasmodium GPIs were found in children with enlarged spleens and a recent episode of severe malaria, but low titers in asymptomatic or uninfected children (França et al, 2017).…”