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Functional human IgA targets a conserved site on malaria sporozoites.
Tan, Joshua; Cho, Hyeseon; Pholcharee, Tossapol; Pereira, Lais S; Doumbo, Safiatou; Doumtabe, Didier; Flynn, Barbara J; Schön, Arne; Kanatani, Sachie; Aylor, Samantha O; Oyen, David; Vistein, Rachel; Wang, Lawrence; Dillon, Marlon; Skinner, Jeff; Peterson, Mary; Li, Shanping; Idris, Azza H; Molina-Cruz, Alvaro; Zhao, Ming; Olano, Lisa Renee; Lee, Patricia J; Roth, Alison; Sinnis, Photini; Barillas-Mury, Carolina; Kayentao, Kassoum; Ongoiba, Aissata; Francica, Joseph R; Traore, Boubacar; Wilson, Ian A; Seder, Robert A; Crompton, Peter D.
Affiliation
  • Tan J; Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD 20852, USA. tanj4@nih.gov pcrompton@niaid.nih.gov.
  • Cho H; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Pholcharee T; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Pereira LS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Doumbo S; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Doumtabe D; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Flynn BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Schön A; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Kanatani S; Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
  • Aylor SO; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Oyen D; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Vistein R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Dillon M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Skinner J; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Peterson M; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Li S; Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Idris AH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Molina-Cruz A; Biological Engineering Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Zhao M; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Olano LR; Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Lee PJ; Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Roth A; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Sinnis P; Department of Drug Discovery, Experimental Therapeutics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Barillas-Mury C; Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
  • Kayentao K; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
  • Ongoiba A; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Francica JR; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Traore B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wilson IA; Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, BP 1805, Point G, Bamako, Mali.
  • Seder RA; Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crompton PD; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sci Transl Med ; 13(599)2021 06 23.
Article in En | MEDLINE | ID: mdl-34162751
ABSTRACT
Immunoglobulin (Ig)A antibodies play a critical role in protection against mucosal pathogens. However, the role of serum IgA in immunity to nonmucosal pathogens, such as Plasmodium falciparum, is poorly characterized, despite being the second most abundant isotype in blood after IgG. Here, we investigated the circulating IgA response in humans to P. falciparum sporozoites that are injected into the skin by mosquitoes and migrate to the liver via the bloodstream to initiate malaria infection. We found that circulating IgA was induced in three independent sporozoite-exposed cohorts individuals living in an endemic region in Mali, malaria-naïve individuals immunized intravenously with three large doses of irradiated sporozoites, and malaria-naïve individuals exposed to a single controlled mosquito bite infection. Mechanistically, we found evidence in an animal model that IgA responses were induced by sporozoites at dermal inoculation sites. From malaria-resistant individuals, we isolated several IgA monoclonal antibodies that reduced liver parasite burden in mice. One antibody, MAD2-6, bound to a conserved epitope in the amino terminus of the P. falciparum circumsporozoite protein, the dominant protein on the sporozoite surface. Crystal structures of this antibody revealed a unique mode of binding whereby two Fabs simultaneously bound either side of the target peptide. This study reveals a role for circulating IgA in malaria and identifies the amino terminus of the circumsporozoite protein as a target of functional antibodies.
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Full text: 1 Database: MEDLINE Main subject: Immunoglobulin A / Antibodies, Protozoan / Malaria Limits: Animals / Humans Language: En Year: 2021 Type: Article
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Immunoglobulin A / Antibodies, Protozoan / Malaria Limits: Animals / Humans Language: En Year: 2021 Type: Article