Virus glycoprotein nanodisc platform for vaccine analytics

Kimmo 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 3rd; James C Paulson; Shane Crotty; Torben Schiffner; Andrew B Ward; William R Schief

doi:10.1038/s41467-026-68985-1

Virus glycoprotein nanodisc platform for vaccine analytics

Nat Commun. 2026 Feb 10;17(1):2561. doi: 10.1038/s41467-026-68985-1.

Authors

Kimmo Rantalainen^{1

2

3}, Alessia Liguori^{1

2

3}, Gabriel Ozorowski^{3

4}, Claudia Flynn^{1

2

3}, Jon M Steichen^{1

2

3}, Olivia M Swanson^{1

2

3

4}, Patrick J Madden^{3

5}, Sabyasachi Baboo⁴, Swastik Phulera⁴, Anant Gharpure⁴, Danny Lu^{1

2

3}, Oleksandr Kalyuzhniy^{1

2

3}, Patrick Skog^{1

2

3}, Sierra Terada^{1

2

3}, Monolina Shil^{3

5}, Jolene K Diedrich⁴, Erik Georgeson^{1

2

3}, Ryan Tingle^{1

2

3}, Saman Eskandarzadeh^{1

2

3}, Wen-Hsin Lee⁴, Nushin Alavi^{1

2

3}, Diana Goodwin^{1

2

3}, Michael Kubitz^{1

2

3}, Sonya Amirzehni^{1

2

3}, Sunny Himansu⁶, Devin Sok^{1

2

3}, Jeong Hyun Lee^{1

2

3}, John R Yates 3rd⁴, James C Paulson^{1

3}, Shane Crotty^{3

5

7}, Torben Schiffner^{8

9

10

11}, Andrew B Ward^{12

13}, William R Schief^{14

15

16

17}

Affiliations

¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
² IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
³ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
⁴ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
⁵ Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, USA.
⁶ Moderna Inc., Cambridge, MA, USA.
⁷ Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
⁸ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. torbens@scripps.edu.
⁹ IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. torbens@scripps.edu.
¹⁰ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. torbens@scripps.edu.
¹¹ Institute for Drug Discovery, Leipzig University Medical Faculty, Leipzig, Germany. torbens@scripps.edu.
¹² Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. andrew@scripps.edu.
¹³ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. andrew@scripps.edu.
¹⁴ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.
¹⁵ IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.
¹⁶ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.
¹⁷ Moderna Inc., Cambridge, MA, USA. schief@scripps.edu.

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.

Publication types

Clinical Trial

MeSH terms

AIDS Vaccines* / chemistry
AIDS Vaccines* / immunology
Antibodies, Neutralizing / immunology
B-Lymphocytes / immunology
Cryoelectron Microscopy
Ebolavirus / immunology
Flow Cytometry
Glycoproteins* / chemistry
Glycoproteins* / immunology
HIV Antibodies / immunology
HIV-1 / immunology
Humans
Nanostructures* / chemistry
Surface Plasmon Resonance
Vaccine Development / methods

Virus glycoprotein nanodisc platform for vaccine analytics

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