Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies

Rory Henderson, Kara Anasti, Kartik Manne, Victoria Stalls, Carrie Saunders, Yishak Bililign, Ashliegh Williams, Pimthada Bubphamala, Maya Montani, Sangita Kachhap, Jingjing Li, Chuancang Jaing, Amanda Newman, Derek W. Cain, Xiaozhi Lu, Sravani Venkatayogi, Madison Berry, Kshitij Wagh, Bette Korber, Kevin O. Saunders, Ming Tian, Fred Alt, Kevin Wiehe, Priyamvada Acharya, S. Munir Alam and Barton F. Haynes ()
Additional contact information
Rory Henderson: Duke University Medical Center
Kara Anasti: Duke University Medical Center
Kartik Manne: Duke University Medical Center
Victoria Stalls: Duke University Medical Center
Carrie Saunders: Duke University Medical Center
Yishak Bililign: Duke University Medical Center
Ashliegh Williams: Duke University Medical Center
Pimthada Bubphamala: Duke University Medical Center
Maya Montani: Duke University Medical Center
Sangita Kachhap: Duke University Medical Center
Jingjing Li: Duke University Medical Center
Chuancang Jaing: Duke University Medical Center
Amanda Newman: Duke University Medical Center
Derek W. Cain: Duke University Medical Center
Xiaozhi Lu: Duke University Medical Center
Sravani Venkatayogi: Duke University Medical Center
Madison Berry: Duke University Medical Center
Kshitij Wagh: Duke University Medical Center
Bette Korber: Los Alamos National Laboratory
Kevin O. Saunders: Duke University Medical Center
Ming Tian: Boston Children’s Hospital
Fred Alt: Boston Children’s Hospital
Kevin Wiehe: Duke University Medical Center
Priyamvada Acharya: Duke University Medical Center
S. Munir Alam: Duke University Medical Center
Barton F. Haynes: Duke University Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identify Env mutations predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encode antibody affinity gains and select for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53120-9 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:15:y:2024:i:1:d:10.1038_s41467-024-53120-9

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

DOI: 10.1038/s41467-024-53120-9

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 ().