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bioRxiv · 10.1101/2024.10.09.617418

A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Completely Protective Multivalent Mucosal Dual Vaccine Against COVID-19 and Flu

Zhu, J.·Sha, J.·Batra, H.·Jain, S.·Wu, X.·Hendrix, E.·Kilgore, P. B.·Sun, K.·Plante, K. S.·Plante, J. A.·Walker, J.·Tao, P.·Chopra, A. K.·Rao, V. B.
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Abstract

A multivalent, rapidly deployable, mucosal vaccine platform is desperately needed to prevent the acquisition and transmission of respiratory infections during epidemics and pandemics. We present one such bacteriophage T4-based platform, and design of dual COVID-19-Flu mucosal vaccines by exploiting its unique architecture. These include: T4s natural affinity for nasal mucosa, flexible engineering to incorporate multiple antigens, and repeat and symmetric epitope presentation for enhanced B cell responses. Hundreds of SARS-CoV-2 spike trimers and nucleocapsid proteins, and influenza hemagglutinin trimers and M2e peptides, were incorporated into a single phage, creating the highest density nanoparticle presentation yet reported. Intranasal administration of adjuvant-free vaccine induced robust mucosal immunity in mice including, neutralizing antibody and secretory IgA, lung-resident CD4+/CD8+ T cells, diverse memory B cells, and complete protection against SARS-CoV-2 and influenza challenges. The noninfectious T4 phage offers an extraordinary platform to rapidly design potent mucosal vaccines against emerging bacterial and viral threats.

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Zhu, J., Sha, J., Batra, H., Jain, S., Wu, X., Hendrix, E., Kilgore, P. B., Sun, K., Plante, K. S., Plante, J. A., Walker, J., Tao, P., Chopra, A. K., Rao, V. B.. 2024-10-09. A Modular Bacteriophage T4 Nanoparticle Platform Enables Rapid Design of Completely Protective Multivalent Mucosal Dual Vaccine Against COVID-19 and Flu. https://doi.org/10.1101/2024.10.09.617418

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