High Antibody Responses against Plasmodium falciparum in Immigrants after Extended Periods of Interrupted Exposure to Malaria

Abstract

BackgroundMalaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas.MethodsA cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142 (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry.ResultsImmigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142 (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria.ConclusionsUpon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures.

Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities

“…2). Linear regression showed that mean antibody response decreased significantly over time after Pf infection (R 2 = 0.23, P < 0.001), consistent with published findings (57,58,(60)(61)(62)(63)(64)(65)(66). To identify antibody responses to Pf antigens that were most informative of an individual's recent exposure to Pf, a flexible prediction method that made few assumptions about the nature of the relationship between Pf exposure and antibody intensity (details in Materials and Methods) was used to algorithmically identify top candidate antigens and model the ability of responses to the selected antigens to predict exposure.…”

Cytokine Profiling in Immigrants with Clinical Malaria after Extended Periods of Interrupted Exposure to Plasmodium falciparum

“…Also, there were no correlations among cytokines/chemokines and antibody responses to P. falciparum antigens [26] in these patients (data not shown).…”

Characterization of posttransfusion Plasmodium falciparum infection in semi‐immune nonparasitemic patients

“…Antibodies to both MSP1 and AMA-1 are known to be relatively protective (growthinhibitory activity) in semi-immune individuals and are responsive to natural parasite stimulation, but they are unlikely to be involved in parasite clearance. 15,16 A weakness of our study is that anti-MSP-1 is probably unrelated to parasite clearance. Other antigens expressed at the surface of parasitized RBCs, such as Pf-erythrocyte membrane protein-1 (PfEMP-1), repetitive interspaced family (RIFIN) protein, or subtelomeric variable open reading frame (STEVOR) proteins, are critical in parasite clearance through immune complex formation.…”

“…This interpretation assumes, probably incorrectly, that anti‐MSP1 is representative of all antibody specificities in a given patient. Antibodies to both MSP1 and AMA‐1 are known to be relatively protective (growth‐inhibitory activity) in semi‐immune individuals and are responsive to natural parasite stimulation, but they are unlikely to be involved in parasite clearance . A weakness of our study is that anti‐MSP‐1 is probably unrelated to parasite clearance.…”