Abstract
BackgroundIn malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. The consequences on pathogen-specific immune responses are not well known. This study evaluated and compared the humoral responses specific to merozoite stage vaccine candidates of Plasmodium falciparum, in children differentially exposed to Anopheles bites in a natural setting.MethodsThe cross-sectional study was carried out in Bouaké (Côte d’Ivoire) where entomological data and blood samples from children (0–14 years) were collected in two sites with similar malaria prevalence. Antibody (IgG, IgG1, IgG3) responses to PfAMA1 and PfMSP1 were evaluated by ELISA. Univariate and multivariate analysis were performed to assess the relationship between the immune responses to P. falciparum antigens and exposure to Anopheles bites in the total cohort and in each site, separately. The individual level of exposure to Anopheles bites was evaluated by quantifying specific IgG response to the Anopheles gSG6-P1 salivary peptide, which represents a proxy of Anopheles exposure.ResultsThe anti-Plasmodium humoral responses were different according to the level of exposure of children, with those highly exposed to Anopheles presenting significantly lower antibody responses to PfMSP1 in total population (IgG and IgG3) and in Petessou village (IgG, IgG1, IgG3). No significant difference was seen for PfAMA1 antigen between children differently exposed to Anopheles. In Dar-es-Salam, a neighbourhood where a high Culex density was reported, children presented very low antibody levels specific to both antigens, and no difference according to the exposure to Anopheles bites was found.ConclusionThese findings may suggest that immunomodulatory components of Anopheles saliva, in addition to other factors, may participate to the modulation of the humoral response specific to Plasmodium merozoite stage antigens. This epidemiological observation may form a starting point for additional work to decipher the role of mosquito saliva on the modulation of the anti-Plasmodium acquired immunity and clinical protection in combining both field and ex vivo immunological studies.
Highlights
In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding
Protective immunity is largely mediated by specific Abs, including immunoglobulin G (IgG) and cytophilic sub-classes (IgG1 and IgG3) [5], that mostly target the P. falciparum blood-stage antigens (Ags), such as apical membrane antigen 1 (PfAMA1) [6], merozoite surface protein 1 and 3 (PfMSP1, PfMSP3) [7, 8], and glutamaterich protein (PfGLURP) [9, 10]
The present study aimed to investigate the relationships between specific Ab responses to merozoite stage antigens (PfMSP1 and PfAMA1) in children differently exposed to Anopheles bites in two study sites in Côte d’Ivoire
Summary
In malaria-endemic areas, human populations are frequently exposed to immunomodulatory salivary components injected during mosquito blood feeding. In malaria-endemic areas, human populations develop natural immunity against P. falciparum that can lead to premunition. This acquired protective immunity takes years to develop after repeated exposure to Plasmodium parasite, is relatively short-lived, and is partially effective. It can efficiently control malaria parasite infection leading to a decline in clinical malaria since low parasitaemia mostly persists in the presence of circulating antibodies (Abs). Protective immunity is largely mediated by specific Abs, including immunoglobulin G (IgG) and cytophilic sub-classes (IgG1 and IgG3) [5], that mostly target the P. falciparum blood-stage antigens (Ags), such as apical membrane antigen 1 (PfAMA1) [6], merozoite surface protein 1 and 3 (PfMSP1, PfMSP3) [7, 8], and glutamaterich protein (PfGLURP) [9, 10]
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