and CP-4/00220 to A

and CP-4/00220 to A.M.); the Agncia de Gesti dAjuts Universitaris i de Recerca (2009SGR934, 2009SGR385, income support 2010FI_B 00168 to J.C.); as well as the Fundacin Ramn Areces. a scientific a malaria event who’ve been 5 years or > 5 years within a non-endemic region. (DOCX) pone.0073624.s004.docx (35K) GUID:?219DF350-DE9F-4600-A126-342B412BCA19 Abstract Background Malaria immunity is often thought to wane in the absence of exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. Methods A 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), na?ve 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 Schisandrin C DBL- were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Results Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P0.026), but no correlation was found between IgG levels and time Schisandrin C 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 (P0.015), similar levels against EBA-175 and DBL-, and lower levels against IEs (P0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P0.001), both with malaria. Conclusions Upon 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. Introduction Maintenance FGF9 of long-term memory responses is critical for achieving protective immunity against many pathogens. The understanding of differential immuno-reactivity to malaria and maintenance of these immune responses is fundamental for the development and design of immunogenic strategies for disease control and eradication. In malaria endemic areas, immunity is acquired gradually with age and continuous exposure, first to severe disease and ultimately to clinical malaria and high parasitemia [1]. Nevertheless, it is thought that upon cessation of exposure to infection immunity wanes rapidly, and this is in contrast with the long-term antibody-mediated immunity that follows one or few exposures to antigens from other infectious microbes [2]. The control of infections is complex, and requires the combined action of antibodies (Ab) and cell-mediated immune responses against both pre-erythrocytic and blood stages; and these two effector mechanisms are required for Schisandrin C both anti-parasitic as well as clinical immunity [3,4]. The relevance of Ab responses in malaria protection was established several decades ago by immunoglobulin G (IgG) passive transfer experiments [5,6], and different mechanisms of immunity have been proposed. Potential Ab effector actions include: blockade of hepatocyte invasion by sporozoites and red blood cell invasion by merozoites; Ab-dependent cellular killing through interaction of target-bound Ab with certain Fc receptors from cell surfaces; opsonization of infected erythrocytes (IE) inducing phagocytic clearance; and neutralization of the parasite glycosylphosphatidylinositol, inhibiting the induction of the inflammatory cytokine cascade [3]. 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 surface protein 1 (MSP-142), and the 175 kDa erythrocyte binding antigen (EBA-175), all three involved in erythrocyte invasion [7C11]. In addition, variant surface antigens (VSA) expressed on IE membranes are also targets of naturally acquired Ab responses associated with immunity [12]. The erythrocyte membrane protein 1 (infection (semi-immune adults), with (n=50) or without clinical malaria (n=27); and (iii) na?ve adults from Schisandrin C a non-endemic area returning from a sub-Saharan Africa malaria endemic region with a first malaria episode (travelers, n=20). Immigrants were recruited at the Tropical Medicine Units of Hospital Clnic de Barcelona (Barcelona, Spain), Hospital Arnau de Vilanova (Lleida, Spain) and.

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