1. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort
- Author
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Gregory Nuel, Paulin Sonon, Adrian J. F. Luty, Gilles Cottrell, Ibrahim Sadissou, André Garcia, Roukiyath Amoussa, Tania d’Almeida, Ambaliou Sanni, Shirley Longacre, D. Courtin, Aziz Bouraima, Florence Migot-Nabias, Rafiou Adamou, Célia Dechavanne, Michael Theisen, Kabirou Moutairou, Edmond J. Remarque, Achille Massougbodji, Jacqueline Milet, Agnès Le Port, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Biochimie et de Biologie Moléculaire (Université d'Abomey Calavi, Cotonou, Bénin) (LBBM), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Universidade de São Paulo = University of São Paulo (USP), Statens Serum Institut [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH), Biomedical Primate Research Centre [Rijswijk] (BPRC), Vaccinologie Parasitaire, Institut Pasteur [Paris] (IP), Laboratoire de Probabilités, Statistique et Modélisation (LPSM (UMR_8001)), Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), This paper describes work undertaken in the context of the PALNOUGENENV, 'Paludisme-Nouvéau-né-Génétique et Environnement', a project supported by Agence Nationale pour la Recherche (projet SEST2006/040/001), Ministère des Affaires Etrangères français (projet REFS No.2006-22) for their financial support. This publication was made possible through the Faculté des Sciences de la Santé (FSS), the Institut des Sciences Biomédicales Appliquées de Cotonou (ISBA), the Programme National de Lutte contre le Paludisme (PNLP) for their institutional support and the Institut de Recherche et de Développment AIRD-ARTS and Ambassade de France à Cotonou (SCAC) for their PhD scholarships to Rafiou ADAMOU and Ibrahim SADISSOU., ANR-06-SEST-0040,PALNOURGENENV,survenue des premières infections palustres chez le noueau-né : déterminants génétiques, biologiques et environnementaux(2006), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), University of Abomey Calavi (UAC), University of São Paulo (USP), University of Copenhagen = Københavns Universitet (KU), Institut Pasteur [Paris], and Laboratoire de Probabilités, Statistiques et Modélisations (LPSM (UMR_8001))
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Male ,Protozoan Proteins ,Antibodies, Protozoan ,MESH: Malaria, Falciparum/immunology ,0302 clinical medicine ,MESH: Pregnancy ,MESH: Antigens, Protozoan/immunology ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Pregnancy ,Surveys and Questionnaires ,Benin ,030212 general & internal medicine ,MESH: Plasmodium falciparum/immunology ,Longitudinal Studies ,Malaria, Falciparum ,MESH: Longitudinal Studies ,MESH: Antibodies, Protozoan/blood ,biology ,Malaria vaccine ,MESH: Infant, Newborn ,MESH: Enzyme-Linked Immunosorbent Assay ,MESH: Infant ,3. Good health ,Infectious Diseases ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Cytophilic IgG ,Female ,Merozoite vaccine candidate antigens ,Antibody ,medicine.symptom ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,030231 tropical medicine ,Plasmodium falciparum ,Context (language use) ,Antigens, Protozoan ,Enzyme-Linked Immunosorbent Assay ,Asymptomatic ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,MESH: Benin ,Antigen ,Immunity ,parasitic diseases ,medicine ,Humans ,lcsh:RC109-216 ,MESH: Surveys and Questionnaires ,MESH: Humans ,business.industry ,Research ,Infant, Newborn ,Infant ,biology.organism_classification ,medicine.disease ,MESH: Protozoan Proteins/immunology ,MESH: Male ,Malaria ,Immunoglobulin G ,Immunology ,biology.protein ,Parasitology ,business ,MESH: Immunoglobulin G/blood ,MESH: Female - Abstract
BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens.METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk.RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition.CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.
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- 2019