Mosaic quadrivalent influenza vaccine single nanoparticle characterization

Area of Science:

• Vaccinology
• Nanotechnology
• Immunology

Background:

• Co-displaying multiple antigens on nanoparticles is crucial for inducing cross-reactive antibodies and broad disease protection.
• A mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for a clinical trial aiming for a universal influenza vaccine.
• Current nanoparticle analysis methods are limited to population analysis, lacking individual nanoparticle valency determination.

Purpose of the Study:

• To confirm the co-display of four distinct influenza haemagglutinin (HA) strains on individual nanoparticles.
• To quantify the valency of mosaic nanoparticles, determining the percentage of nanoparticles displaying two, three, or four HA proteins.
• To establish and validate integrated imaging and physicochemical methods for single nanoparticle multivalency analysis.

Main Methods:

• Total internal reflection fluorescence microscopy (TIRFM) was employed for single nanoparticle imaging.
• Supportive physical-chemical methods were utilized to corroborate TIRFM findings.
• Development of integrated imaging and physicochemical techniques for assessing nanoparticle multivalency.

Main Results:

• Demonstrated for the first time that single nanoparticles successfully co-display four distinct influenza HA antigens.
• Quantified the percentages of multivalent nanoparticles, identifying those with two, three, or four HA proteins.
• Validated novel methods for analyzing single nanoparticle antigen composition.

Conclusions:

• The developed FluMos-v1 vaccine achieves the co-display of multiple HA antigens on individual nanoparticles.
• The established single nanoparticle analysis methods provide crucial insights into nanoparticle composition.
• These methods will aid in understanding the immunogenicity data from the ongoing FluMos-v1 clinical trial and future vaccine development.