Virus glycoprotein nanodisc platform for vaccine design

Area of Science:

• Structural biology
• Vaccine development
• Virology

Background:

• Transmembrane glycoproteins are crucial vaccine targets.
• Current methods for analyzing these antigens often use soluble proteins, limiting insights.
• mRNA-LNP technology enables in situ protein production but requires suitable antigen formats for study.

Purpose of the Study:

• To present a platform for assembling transmembrane glycoprotein vaccine candidates into lipid nanodiscs.
• To demonstrate the utility of these nanodiscs for studying HIV membrane proximal external region (MPER) immunogens.
• To provide a tool for accelerating next-generation viral vaccine development.

Main Methods:

• Assembling transmembrane glycoproteins into lipid nanodiscs.
• Utilizing surface plasmon resonance (SPR) for binding assays.
• Employing fluorescence-activated cell sorting (FACS) for ex vivo B cell analysis.
• Determining high-resolution structures using cryogenic electron microscopy (cryo-EM).

Main Results:

• Successfully assembled transmembrane glycoprotein vaccine candidates into nanodiscs.
• Demonstrated nanodisc utility in HIV MPER vaccine development through binding assays and B cell sorting.
• Determined the structure of an HIV MPER immunogen nanodisc complexed with broadly neutralizing antibodies (bnAbs) to 3.5 Å.
• Provided a structural template for MPER-based immunogen design.

Conclusions:

• The lipid nanodisc platform is effective for characterizing transmembrane viral antigens.
• This platform facilitates structure-based immunogen design for MPER and potentially other viral targets.
• The methodology accelerates the development of advanced viral vaccines.