skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.immuni.2017.11.007

Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science

Save / Share:

Works referencing / citing this record:

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite
journal, March 2018

  • Kisalu, Neville K.; Idris, Azza H.; Weidle, Connor
  • Nature Medicine, Vol. 24, Issue 4
  • DOI: 10.1038/nm.4512

A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein
journal, March 2018

  • Tan, Joshua; Sack, Brandon K.; Oyen, David
  • Nature Medicine, Vol. 24, Issue 4
  • DOI: 10.1038/nm.4513

Human adaptive immune receptor repertoire analysis-Past, present, and future
journal, June 2018

  • Nielsen, Sandra C. A.; Boyd, Scott D.
  • Immunological Reviews, Vol. 284, Issue 1
  • DOI: 10.1111/imr.12667

Assessing human B cell repertoire diversity and convergence
journal, June 2018

  • Imkeller, Katharina; Wardemann, Hedda
  • Immunological Reviews, Vol. 284, Issue 1
  • DOI: 10.1111/imr.12670

Disordered epitopes as peptide vaccines
journal, April 2018

  • MacRaild, Christopher A.; Seow, Jeffrey; Das, Sreedam C.
  • Peptide Science, Vol. 110, Issue 3
  • DOI: 10.1002/pep2.24067

Recombinant measles vaccine expressing malaria antigens induces long-term memory and protection in mice
journal, February 2019


Antibodies against Plasmodium falciparum malaria at the molecular level
journal, August 2019


Malaria prevention: from immunological concepts to effective vaccines and protective antibodies
journal, October 2018


Adenovirus-prime and baculovirus-boost heterologous immunization achieves sterile protection against malaria sporozoite challenge in a murine model
journal, March 2018


Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection
journal, November 2017

  • Scally, Stephen W.; Murugan, Rajagopal; Bosch, Alexandre
  • Journal of Experimental Medicine, Vol. 215, Issue 1
  • DOI: 10.1084/jem.20170869

Controlled Human Malaria Infection of Healthy Adults With Lifelong Malaria Exposure to Assess Safety, Immunogenicity, and Efficacy of the Asexual Blood Stage Malaria Vaccine Candidate GMZ2
journal, December 2018

  • Dejon-Agobe, Jean Claude; Ateba-Ngoa, Ulysse; Lalremruata, Albert
  • Clinical Infectious Diseases, Vol. 69, Issue 8
  • DOI: 10.1093/cid/ciy1087

B‐cell memory in malaria: Myths and realities
journal, November 2019

  • Pérez‐Mazliah, Damián; Ndungu, Francis M.; Aye, Racheal
  • Immunological Reviews, Vol. 293, Issue 1
  • DOI: 10.1111/imr.12822

Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites
journal, December 2019

  • Jong, Roos M.; Tebeje, Surafel K.; Meerstein‐Kessel, Lisette
  • Immunological Reviews, Vol. 293, Issue 1
  • DOI: 10.1111/imr.12828

Cryo-EM structure of P. falciparum circumsporozoite protein with a vaccine-elicited antibody is stabilized by somatically mutated inter-Fab contacts
journal, October 2018

  • Oyen, David; Torres, Jonathan L.; Cottrell, Christopher A.
  • Science Advances, Vol. 4, Issue 10
  • DOI: 10.1126/sciadv.aau8529

Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope
journal, June 2018

  • Imkeller, Katharina; Scally, Stephen W.; Bosch, Alexandre
  • Science, Vol. 360, Issue 6395
  • DOI: 10.1126/science.aar5304

Clonal selection drives protective memory B cell responses in controlled human malaria infection
journal, February 2018


B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets
journal, May 2019


Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites
journal, August 2018

  • Marin-Mogollon, Catherin; van Pul, Fiona J. A.; Miyazaki, Shinya
  • Malaria Journal, Vol. 17, Issue 1
  • DOI: 10.1186/s12936-018-2431-1

Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein
journal, March 2020


Getting in: The structural biology of malaria invasion
journal, September 2019


Combination of RTS,S and Pfs25-IMX313 Induces a Functional Antibody Response Against Malaria Infection and Transmission in Mice
journal, December 2018


Development of B Cell Memory in Malaria
journal, April 2019


Qualified Biolayer Interferometry Avidity Measurements Distinguish the Heterogeneity of Antibody Interactions with Plasmodium falciparum Circumsporozoite Protein Antigens
journal, July 2018

  • Dennison, S. Moses; Reichartz, Matthew; Seaton, Kelly E.
  • The Journal of Immunology, Vol. 201, Issue 4
  • DOI: 10.4049/jimmunol.1800323

Designer Parasites: Genetically Engineered Plasmodium as Vaccines To Prevent Malaria Infection
journal, December 2018

  • Goswami, Debashree; Minkah, Nana K.; Kappe, Stefan H. I.
  • The Journal of Immunology, Vol. 202, Issue 1
  • DOI: 10.4049/jimmunol.1800727