6VTW

De novo protein design enables the precise induction of RSV-neutralizing antibodies

Summary for 6VTW

• Entry DOI: 10.2210/pdb6vtw/pdb
• Descriptor: S4_2.45, 101F Fab Light Chain, 101F Fab Heavy Chain, ... (4 entities in total)
• Functional Keywords: de novo designed, immunogens, antibodies, in vivo, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 52477.77

Authors

Jardetzky, T.,Correia, B. (deposition date: 2020-02-13, release date: 2020-04-15, Last modification date: 2024-10-30)

Primary citation

Sesterhenn, F.,Yang, C.,Bonet, J.,Cramer, J.T.,Wen, X.,Wang, Y.,Chiang, C.I.,Abriata, L.A.,Kucharska, I.,Castoro, G.,Vollers, S.S.,Galloux, M.,Dheilly, E.,Rosset, S.,Corthesy, P.,Georgeon, S.,Villard, M.,Richard, C.A.,Descamps, D.,Delgado, T.,Oricchio, E.,Rameix-Welti, M.A.,Mas, V.,Ervin, S.,Eleouet, J.F.,Riffault, S.,Bates, J.T.,Julien, J.P.,Li, Y.,Jardetzky, T.,Krey, T.,Correia, B.E.
De novo protein design enables the precise induction of RSV-neutralizing antibodies.
Science, 368:-, 2020

PubMed Abstract: De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a protein design algorithm called TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. In both mice and nonhuman primates, cocktails of three de novo-designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused preexisting antibody responses toward defined neutralization epitopes. Overall, our design approach opens the possibility of targeting specific epitopes for the development of vaccines and therapeutic antibodies and, more generally, will be applicable to the design of de novo proteins displaying complex functional motifs.

PubMed: 32409444
DOI: 10.1126/science.aay5051

Experimental method

X-RAY DIFFRACTION (2.6 Å)