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The Plasmodium vivax Duffy-binding protein (DBP) is a prime target of the protective immune response and a promising vaccine candidate for P. vivax malaria. Naturally acquired immunity (NAI) protects against malaria in adults residing in infection-endemic regions, and the passive transfer of malarial immunity confers protection. A vaccine that replicates NAI will effectively prevent disease. Here, we report the structures of DBP region II in complex with human-derived, neutralizing monoclonal antibodies obtained from an individual in a malaria-endemic area with NAI. We identified protective epitopes using X-ray crystallography, hydrogen-deuterium exchange mass spectrometry, mutational mapping and P. vivax invasion studies. These approaches reveal that naturally acquired human antibodies neutralize P. vivax by targeting the binding site for Duffy antigen receptor for chemokines (DARC) and the dimer interface of P. vivax DBP. Antibody binding is unaffected by polymorphisms in the vicinity of epitopes, suggesting that the antibodies have evolved to engage multiple polymorphic variants of DBP. The human antibody epitopes are broadly conserved and are distinct from previously defined epitopes for broadly conserved murine monoclonal antibodies. A library of globally conserved epitopes of neutralizing human antibodies offers possibilities for rational design of strain-transcending DBP-based vaccines and therapeutics against P. vivax.
Pubmed ID: 31133752
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Registry and results database of federally and privately supported clinical trials conducted in United States and around world. Provides information about purpose of trial, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.Offers information for locating federally and privately supported clinical trials for wide range of diseases and conditions. Research study in human volunteers to answer specific health questions. Interventional trials determine whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments. Observational trials address health issues in large groups of people or populations in natural settings. ClinicalTrials.gov contains trials sponsored by National Institutes of Health, other federal agencies, and private industry. Studies listed in database are conducted in all 50 States and in 178 countries.
View all literature mentionsA high-quality integrated knowledge resource specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrate species, and in the immunoglobulin superfamily (IgSF), MHC superfamily (MhcSF) and related proteins of the immune system (RPI) of vertebrates and invertebrates, serving as the global reference in immunogenetics and immunoinformatics. IMGT provides a common access to sequence, genome and structure Immunogenetics data, based on the concepts of IMGT-ONTOLOGY and on the IMGT Scientific chart rules. IMGT works in close collaboration with EBI (Europe), DDBJ (Japan) and NCBI (USA). IMGT consists of sequence databases, genome database, structure database, and monoclonal antibodies database, Web resources and interactive tools.
View all literature mentionsA structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.
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