Nano-Assembled Polyphosphazene Delivery System Enables Effective Intranasal Immunization with Nipah Virus Subunit...

Area of Science:

• Nanotechnology
• Vaccinology
• Virology

Background:

• Nipah virus poses a lethal threat, necessitating vaccines targeting the respiratory tract entry point.
• Intranasal vaccines are attractive for inducing both systemic and mucosal immunity against respiratory pathogens.
• The Hendra virus attachment glycoprotein is a potential subunit antigen for Nipah and Hendra virus vaccines.

Purpose of the Study:

• To develop and characterize a polyphosphazene-based intranasal vaccine delivery system for Nipah virus.
• To evaluate the immunogenicity and efficacy of the polyphosphazene-enabled Nipah vaccine candidate in a preclinical model.
• To compare the immune response induced by the novel vaccine with a clinically relevant alum-adjuvanted vaccine.

Main Methods:

• Self-assembly of polyphosphazene with Hendra virus glycoprotein into nanoscale supramolecular constructs.
• Characterization of nanoconstructs using cryogenic electron microscopy, asymmetric flow field flow fractionation, dynamic light scattering, fluorescence spectrophotometry, and turbidimetric titration.
• Immunization of hamsters with the polyphosphazene-nanoparticle vaccine and assessment of immune responses, including total IgG and neutralizing antibodies.

Main Results:

• Polyphosphazene formed nanoscale supramolecular constructs with the viral glycoprotein, capable of signaling through Toll-like receptor 7/8 and interacting with mucin.
• The nanoconstructs were successfully visualized using cryogenic electron microscopy.
• The intranasal polyphosphazene-Nipah vaccine candidate induced superior total IgG and neutralizing antibody responses in hamsters compared to the alum-adjuvanted vaccine.

Conclusions:

• Polyphosphazene-based nanoassemblies are effective delivery vehicles for intranasal vaccines.
• This nanotechnology holds significant potential for developing advanced vaccines against Nipah virus and other respiratory pathogens.
• The developed vaccine candidate demonstrated promising immunogenicity and warrants further investigation for clinical application.