| Autor: |
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, Barton F. Haynes |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-53120-9 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink