Engaging an HIV vaccine target through the acquisition of low B cell affinity

Larance Ronsard, Ashraf S. Yousif, Faez Amokrane Nait Mohamed, Jared Feldman, Vintus Okonkwo, Caitlin McCarthy, Julia Schnabel, Timothy Caradonna, Ralston M. Barnes, Daniel Rohrer, Nils Lonberg, Aaron Schmidt and Daniel Lingwood ()
Additional contact information
Larance Ronsard: The Massachusetts Institute of Technology and Harvard University
Ashraf S. Yousif: The Massachusetts Institute of Technology and Harvard University
Faez Amokrane Nait Mohamed: The Massachusetts Institute of Technology and Harvard University
Jared Feldman: The Massachusetts Institute of Technology and Harvard University
Vintus Okonkwo: The Massachusetts Institute of Technology and Harvard University
Caitlin McCarthy: The Massachusetts Institute of Technology and Harvard University
Julia Schnabel: The Massachusetts Institute of Technology and Harvard University
Timothy Caradonna: The Massachusetts Institute of Technology and Harvard University
Ralston M. Barnes: Bristol-Myers Squibb
Daniel Rohrer: Bristol-Myers Squibb
Nils Lonberg: Bristol-Myers Squibb
Aaron Schmidt: The Massachusetts Institute of Technology and Harvard University
Daniel Lingwood: The Massachusetts Institute of Technology and Harvard University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40918-2 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_s41467-023-40918-2

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

DOI: 10.1038/s41467-023-40918-2

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 ().