bioRxiv : the preprint server for biology · 2025
Virus glycoprotein nanodisc platform for vaccine design.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Rantalainen Kimmo, Liguori Alessia, Ozorowski Gabriel, Flynn Claudia, Steichen Jon M, Swanson Olivia, Madden Patrick J, Baboo Sabyasachi, Phulera Swastik, Gharpure Anant, Lu Danny, Kalyuzhniy Oleksandr, Skog Patrick, Terada Sierra, Shil Monolina, Diedrich Jolene K, Georgeson Erik, Tingle Ryan, Eskandarzadeh Saman, Lee Wen-Hsin, Alavi Nushin, Goodwin Diana, Kubitz Michael, Amirzehni Sonya, Himansu Sunny, Sok Devin, Lee Jeong Hyun, Yates John R, Paulson James C, Crotty Shane, Schiffner Torben, Ward Andrew B, Schief William R
Аннотация
Transmembrane glycoproteins of enveloped viruses are the targets of neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in situ production of transmembrane glycoproteins upon immunization, but biophysical characterization of transmembrane antigens and in vitro analysis of post-immunization antibody responses typically rely on soluble proteins. Here, we present a methodological platform for assembling transmembrane glycoprotein vaccine candidates into lipid nanodiscs. We demonstrate the utility of the nanodiscs in HIV membrane proximal external region (MPER)-targeting vaccine development by binding assays using surface plasmon resonance (SPR), ex vivo B cell sorting with fluorescence-activated cell sorting (FACS), and by determining the structure of a prototypical HIV MPER-targeting immunogen nanodisc in complex with three broadly neutralizing antibodies (bnAbs), including the MPER bnAb 10E8, to 3.5 Å by cryogenic electron microscopy (cryo-EM), providing a template for structure-based immunogen design for MPER. Overall, the platform offers a tool for accelerating the development of next-generation viral vaccines.