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<p>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.</p>

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Virus glycoprotein nanodisc platform for vaccine analytics

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月10日

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  • 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 III,
  • James C. Paulson,
  • Shane Crotty,
  • Torben Schiffner,
  • Andrew B. Ward,
  • William R. Schief

摘要

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.