Bioengineered Norovirus S₆₀ Nanoparticles as a Multifunctional Vaccine Platform

Area of Science:

• Structural biology
• Virology
• Vaccine development
• Nanotechnology

Background:

• Viral capsid proteins commonly self-assemble through homotypic interactions.
• Norovirus shell (S) domain naturally forms interior capsid shells.
• Developing robust platforms for antigen presentation is crucial for vaccine design.

Purpose of the Study:

• To engineer a 60-valent icosahedral nanoparticle (S60) using the norovirus S domain.
• To create a versatile platform for antigen presentation and vaccine development.
• To evaluate the immunogenicity and efficacy of S60-based vaccines.

Main Methods:

• Genetically modified the norovirus S domain with an R69A mutation and triple cysteine mutations (V57C/Q58C/S136C).
• Produced S60 nanoparticles in E. coli.
• Constructed chimeric S60 nanoparticles displaying rotavirus (RV) VP8* antigens.
• Assessed nanoparticle structure, antigenicity, immunogenicity in mice, and neutralizing activity.

Main Results:

• Successfully produced 60-valent, icosahedral S60 nanoparticles with enhanced stability via disulfide bonds.
• S60-VP8* nanoparticles elicited high IgG responses against rotavirus VP8* in mice.
• Antisera demonstrated significant blockade of VP8* binding and neutralization of RV infection.
• Determined the three-dimensional structures of S60 and S60-VP8* particles.

Conclusions:

• The engineered S60 nanoparticle is a highly effective platform for antigen presentation and vaccine development.
• The intermolecular disulfide bond strategy can stabilize viral-like particles for antigen display.
• The S60 nanoparticle platform shows promise for developing vaccines against various infectious agents.