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A Molecular Analysis of Memory B Cell and Antibody Responses Against Plasmodium falciparum Merozoite Surface Protein 1 in Children and Adults From Uganda.
Gonzales, S Jake; Clarke, Kathleen N; Batugedara, Gayani; Garza, Rolando; Braddom, Ashley E; Reyes, Raphael A; Ssewanyana, Isaac; Garrison, Kendra C; Ippolito, Gregory C; Greenhouse, Bryan; Bol, Sebastiaan; Bunnik, Evelien M.
  • Gonzales SJ; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Clarke KN; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Batugedara G; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Garza R; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Braddom AE; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Reyes RA; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
  • Ssewanyana I; Infectious Disease Research Collaboration, Kampala, Uganda.
  • Garrison KC; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  • Ippolito GC; Department of Chemical Engineering, University of Texas at Austin, Austin, TX, United States.
  • Greenhouse B; Department of Molecular Biosciences and Department of Oncology, Dell Medical School, University of Texas at Austin, Austin, TX, United States.
  • Bol S; Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
  • Bunnik EM; Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Front Immunol ; 13: 809264, 2022.
Article in English | MEDLINE | ID: covidwho-1979036
ABSTRACT
Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Merozoite Surface Protein 1 / Malaria Type of study: Experimental Studies / Randomized controlled trials Topics: Variants Limits: Adult / Animals / Child / Humans Country/Region as subject: Africa Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.809264

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Merozoite Surface Protein 1 / Malaria Type of study: Experimental Studies / Randomized controlled trials Topics: Variants Limits: Adult / Animals / Child / Humans Country/Region as subject: Africa Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.809264