Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.

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  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4172 (Electronic) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE
    • Publication Information:
      Publication: Cambridge, Ma : Cell Press
      Original Publication: Cambridge, MIT Press.
    • Subject Terms:
      Antibodies, Neutralizing*/immunology ; Plasmodium falciparum*/immunology ; Malaria, Falciparum*/immunology ; Malaria, Falciparum*/prevention & control ; Malaria, Falciparum*/parasitology ; Malaria Vaccines*/immunology ; Antibodies, Protozoan*/immunology ; Antigens, Protozoan*/immunology; Humans ; Immunoglobulin G/immunology ; Immunoglobulin G/blood ; Protozoan Proteins/immunology ; Antibodies, Monoclonal/immunology ; Adult ; B-Lymphocytes/immunology ; Epitopes/immunology ; Female ; Mali ; Carrier Proteins/immunology ; Male ; Adolescent
    • Abstract:
      Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.
      Competing Interests: Declaration of interests J.T., L.T.W., and A.J.R.C. are co-inventors on a provisional patent filed on the mAbs described in this study. J.R.B., K.M., M.K.H., and S.J.D. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. A.M.M. has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies. The content of this publication does not necessarily reflect the views or policies of the DHHS or of the institutions and companies with which the authors are affiliated.
      (Published by Elsevier Inc.)
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    • Grant Information:
      United Kingdom WT_ Wellcome Trust
    • Contributed Indexing:
      Keywords: Plasmodium falciparum; RH5; malaria; monoclonal antibodies; natural infection; vaccine design
    • Accession Number:
      0 (Antibodies, Neutralizing)
      0 (Malaria Vaccines)
      0 (RH5 protein, Plasmodium falciparum)
      0 (Antibodies, Protozoan)
      0 (Antigens, Protozoan)
      0 (Immunoglobulin G)
      0 (Protozoan Proteins)
      0 (Antibodies, Monoclonal)
      0 (Epitopes)
      0 (Carrier Proteins)
    • Publication Date:
      Date Created: 20240726 Date Completed: 20240906 Latest Revision: 20240912
    • Publication Date:
      20250114
    • Accession Number:
      PMC11383431
    • Accession Number:
      10.1016/j.cell.2024.06.037
    • Accession Number:
      39059381