Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

Triller, Gianna; Scally, Stephen W.; Costa, Giulia; Pissarev, Maria; Kreschel, Cornelia; Bosch, Alexandre; Marois, Eric; Sack, Brandon K.; Murugan, Rajagopal; Salman, Ahmed M.; Janse, Chris J.; Khan, Shahid M.; Kappe, Stefan H. I.; Adegnika, Ayola A.; Mordmüller, Benjamin; Levashina, Elena A.; Julien, Jean-Philippe; Wardemann, Hedda

doi:10.1016/j.immuni.2017.11.007

Title: Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

Journal Article · Wed Nov 29 00:00:00 EST 2017 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2017.11.007· OSTI ID:1488319

Triller, Gianna; Scally, Stephen W.; Costa, Giulia; Pissarev, Maria; Kreschel, Cornelia; Bosch, Alexandre; Marois, Eric; Sack, Brandon K.; Murugan, Rajagopal; Salman, Ahmed M.; Janse, Chris J.; Khan, Shahid M.; Kappe, Stefan H. I.; Adegnika, Ayola A.; Mordmüller, Benjamin; Levashina, Elena A.; Julien, Jean-Philippe; Wardemann, Hedda

Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but protective humoral immunity is difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. We report NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC); International Max Planck Research School for Infectious Diseases and Immunology (IMPRS-IDI); German National Academic Foundation; Canada Foundation for Innovation (CFI); Natural Sciences and Engineering Research Council of Canada (NSERC); University of Saskatchewan; Government of Saskatchewan; Western Economic Diversification Canada; National Research Council Canada (NRC); Canadian Institutes of Health Research (CIHR); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; F32 AI 114113

OSTI ID:: 1488319

Alternate ID(s):: OSTI ID: 1432855

Journal Information:: Immunity, Journal Name: Immunity Vol. 47 Journal Issue: 6; ISSN 1074-7613

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 93 works

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59 BASIC BIOLOGICAL SCIENCES
Plasmodium falciparum
malaria
natural infection
circumsporozoite protein
human
memory B cells
protective antibodies
X-ray structures
epitope specificity
affinity maturation

Title: Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

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