Virus glycoprotein nanodisc platform for vaccine analytics
Abstract
Abstract Transmembrane glycoproteins of enveloped viruses are targets of neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in vivo expression of transmembrane glycoproteins, but in vitro biophysical characterization of transmembrane antigens and analysis of post-immunization antibody responses typically rely on soluble proteins. Here, we present a platform for assembling transmembrane glycoprotein vaccine candidates into lipid nanodiscs. We demonstrate the utility of 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 MPER bnAb 10E8, to 3.5 Å by cryogenic electron microscopy (cryo-EM), providing a template for structure-based immunogen design. To demonstrate general applicability we characterize Ebola virus glycoprotein nanodiscs. Overall, the platform offers a tool for accelerating development of next-generation vaccines.
Article Details
Authors (33)
Kimmo Rantalainen
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute
Alessia Liguori
Gabriel Ozorowski
Claudia Flynn
Jon M. Steichen
Olivia M. Swanson
Patrick J. Madden
Sabyasachi Baboo
Swastik Phulera
Anant Gharpure
Danny Lu
Oleksandr Kalyuzhniy
Patrick Skog
Sierra Terada
Department of Immunology and Microbiology, The Scripps Research Institute
Monolina Shil
Jolene K. Diedrich
Erik Georgeson
Ryan Tingle
Saman Eskandarzadeh
Department of Immunology and Microbiology, The Scripps Research Institute
Wen-Hsin Lee
Nushin Alavi
Diana Goodwin
Michael Kubitz
Center for HIV/AIDS Vaccine Development, The Scripps Research Institute
Sonya Amirzehni
Department of Immunology and Microbiology, The Scripps Research Institute
Sunny Himansu
Devin Sok
Jeong Hyun Lee
John R. Yates
James C. Paulson
Shane Crotty
Torben Schiffner
Andrew B. Ward
William R. Schief