Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies
Abstract
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.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- 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)
- OSTI Identifier:
- 1488319
- Alternate Identifier(s):
- OSTI ID: 1432855
- Grant/Contract Number:
- AC02-06CH11357; F32 AI 114113
- Resource Type:
- Published Article
- Journal Name:
- Immunity
- Additional Journal Information:
- Journal Name: Immunity Journal Volume: 47 Journal Issue: 6; Journal ID: ISSN 1074-7613
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Plasmodium falciparum; malaria; natural infection; circumsporozoite protein; human; memory B cells; protective antibodies; X-ray structures; epitope specificity; affinity maturation
Citation Formats
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, and Wardemann, Hedda. Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies. United States: N. p., 2017.
Web. doi:10.1016/j.immuni.2017.11.007.
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. Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies. United States. doi:10.1016/j.immuni.2017.11.007.
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, and Wardemann, Hedda. Wed .
"Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies". United States. doi:10.1016/j.immuni.2017.11.007.
@article{osti_1488319,
title = {Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies},
author = {Triller, Gianna and Scally, Stephen W. and Costa, Giulia and Pissarev, Maria and Kreschel, Cornelia and Bosch, Alexandre and Marois, Eric and Sack, Brandon K. and Murugan, Rajagopal and Salman, Ahmed M. and Janse, Chris J. and Khan, Shahid M. and Kappe, Stefan H. I. and Adegnika, Ayola A. and Mordmüller, Benjamin and Levashina, Elena A. and Julien, Jean-Philippe and Wardemann, Hedda},
abstractNote = {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.},
doi = {10.1016/j.immuni.2017.11.007},
journal = {Immunity},
number = 6,
volume = 47,
place = {United States},
year = {2017},
month = {11}
}
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DOI: 10.1016/j.immuni.2017.11.007
DOI: 10.1016/j.immuni.2017.11.007
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Works referencing / citing this record:
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