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TitleVirus glycoprotein nanodisc platform for vaccine analytics.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateFeb 10, 2026
AuthorsKimmo Rantalainen / 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 / Monolina Shil / Jolene K Diedrich / Erik Georgeson / Ryan Tingle / Saman Eskandarzadeh / Wen-Hsin Lee / Nushin Alavi / Diana Goodwin / Michael Kubitz / Sonya Amirzehni / Sunny Himansu / Devin Sok / Jeong Hyun Lee / John R Yates / James C Paulson / Shane Crotty / Torben Schiffner / Andrew B Ward / William R Schief /
PubMed AbstractTransmembrane glycoproteins of enveloped viruses are targets of neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in vivo expression of transmembrane glycoproteins, ...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.
External linksNat Commun / PubMed:41667448 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 4.3 Å
Structure data

70469

9ogl

EMDB-70469, PDB-9ogl:
BG505 MD39.3 SOSIP.664 in complex with 3BC315, BG18 and VRC01 Fabs
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-70470: BG505 MD39.3 Env gp151 MPER nanodisc in complex with 10E8, BG18 and VRC01 Fabs (2x 10E8 Fabs)
Method: EM (single particle) / Resolution: 4.3 Å

70471

9ogm

EMDB-70471, PDB-9ogm:
BG505 MD39.3 Env gp151 MPER nanodisc in complex with 10E8, BG18 and VRC01 Fabs (1x 10E8 Fab)
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/Immune System / MPER / HIV-1 / gp41 / broadly neutralizing antibody / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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