High antibody responses against Plasmodium falciparum in immigrants after extended periods of interrupted exposure to malaria.

Gemma Moncunill,Alfons Jiménez,Carlota Dobaño,Joseph J Campo,Chetan E Chitnis,Mercè Almirall,Laura Puyol,Evelina Angov,Alfredo Mayor,Ruth Aguilar,Pedro L Alonso,Cristina Soler,Núria Casas-Vila,Azucena Bardají,Augusto Nhabomba,Joaquím Gascón ,Maria Nélia Manaca ,María Jesús Pinazo ,José Muñóz ,Sandeep Dutta

doi:10.1371/journal.pone.0073624

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.

Highlights

Maintenance of long-term memory responses is critical for achieving protective immunity against many pathogens
In this study we found that after long periods without continuous malaria exposure, immigrants from endemic areas without malaria still presented seropositivities of 32% to 98% for erythrocytic antigens considered as leading vaccine candidates, and immigrants with clinical malaria had similar seroprevalences than semi-immune adults with a clinical episode immigrants without malaria had lower levels of immunoglobulin G (IgG) to all antigens tested compared to healthy adults with continuous life-long exposure to malaria
This may suggest that there is some loss of immunity, in this cohort we did not observe an association between time since migration and Ab levels, which may indicate that IgG are longer-lived than usually perceived, at least in adults

Summary

Introduction

Maintenance of long-term memory responses is critical for achieving protective immunity against many pathogens. The control of P. falciparum infections is complex, and requires the combined action of antibodies (Ab) and cellmediated immune responses against both pre-erythrocytic and blood stages; and these two effector mechanisms are required for both anti-parasitic as well as clinical immunity [3,4]. P. falciparum antigens targeted by naturally acquired IgG associated with immunity include the merozoite proteins: apical membrane antigen 1 (AMA-1), the 42-kDa fragment from the C terminus of merozoite surface protein 1 (MSP-142), and the 175 kDa erythrocyte binding antigen (EBA-175), all three involved in erythrocyte invasion [7,8,9,10,11]. 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

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