Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection

Gregory M. Martin, Jonathan L. Torres, Tossapol Pholcharee, David Oyen, Yevel Flores-Garcia, Grace Gibson, Re’em Moskovitz, Nathan Beutler, Diana D. Jung, Jeffrey Copps, Wen-Hsin Lee, Gonzalo Gonzalez-Paez, Daniel Emerling, Randall S. MacGill, Emily Locke, C. Richter King, Fidel Zavala, Ian A. Wilson and Andrew B. Ward ()
Additional contact information
Gregory M. Martin: The Scripps Research Institute
Jonathan L. Torres: The Scripps Research Institute
Tossapol Pholcharee: The Scripps Research Institute
David Oyen: The Scripps Research Institute
Yevel Flores-Garcia: Johns Hopkins Bloomberg School of Public Health
Grace Gibson: The Scripps Research Institute
Re’em Moskovitz: The Scripps Research Institute
Nathan Beutler: The Scripps Research Institute
Diana D. Jung: The Scripps Research Institute
Jeffrey Copps: The Scripps Research Institute
Wen-Hsin Lee: The Scripps Research Institute
Gonzalo Gonzalez-Paez: The Scripps Research Institute
Daniel Emerling: Atreca Inc
Randall S. MacGill: PATH’s Malaria Vaccine Initiative
Emily Locke: PATH’s Malaria Vaccine Initiative
C. Richter King: PATH’s Malaria Vaccine Initiative
Fidel Zavala: Johns Hopkins Bloomberg School of Public Health
Ian A. Wilson: The Scripps Research Institute
Andrew B. Ward: The Scripps Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3–33 antibodies and highlight key features underlying the potent protection of this antibody family.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40151-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40151-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40151-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().