Tobacco Mosaic Virus as a mucosal delivery platform for an intranasal vaccine against Pseudomonas aeruginosa

Summary

Development of an intranasal vaccine against Pseudomonas aeruginosa using Tobacco Mosaic Virus as a mucosal delivery platform to provide broad protection against various strains.

What they want

This project focuses on developing a multi-valent intranasal protein subunit vaccine against Pseudomonas aeruginosa (PA) utilizing tobacco mosaic virus (TMV) as a delivery platform. The work involves defining additional vaccine antigens to create a multi-valent vaccine for broad protection against multiple PA strains and identifying the mechanism(s) of vaccine-mediated protection to enhance efficacy. Preliminary studies demonstrated protection in mice using intranasal vaccination with TMV conjugated to PcrV, the tip protein of the PA type III secretion system, in the presence of the Th17 skewing adjuvant curdlan.

Deliverables

Defined additional vaccine antigens for a multi-valent vaccine
A multi-valent vaccine providing broad protection against multiple strains of PA
Identified mechanism(s) of vaccine-mediated protection
An effective mucosal vaccine for use in at-risk patients

Technical requirements

Use of Tobacco Mosaic Virus (TMV) as a mucosal delivery platform
Development of an intranasal protein subunit vaccine
Recombinant TMV expressing a surface-exposed lysine on the coat protein for antigen conjugation
Conjugation of vaccine antigens (e.g., PcrV) to the viral surface
Use of Th17 skewing adjuvant (e.g., curdlan)
Assessment of protection against lethal respiratory challenge with PA
Measurement of anti-PcrV antibody production
Measurement of elevated IL-17 and IFNγ in lungs and spleens