Bacteriophage T4 as a Protein-Based, Adjuvant- and Needle-Free, Mucosal Pandemic Vaccine Design Platform

Abstract

The COVID-19 pandemic has transformed vaccinology. Rapid deployment of mRNA vaccines has saved countless lives. However, these platforms have inherent limitations including lack of durability of immune responses and mucosal immunity, high cost, and thermal instability. These and uncertainties about the nature of future pandemics underscore the need for exploring next-generation vaccine platforms. Here, we present a novel protein-based, bacteriophage T4 platform for rapid design of efficacious vaccines against bacterial and viral pathogens. Full-length antigens can be displayed at high density on a 120 × 86 nm phage capsid through nonessential capsid binding proteins Soc and Hoc. Such nanoparticles, without any adjuvant, induce robust humoral, cellular, and mucosal responses when administered intranasally and confer sterilizing immunity. Combined with structural stability and ease of manufacture, T4 phage provides an excellent needle-free, mucosal pandemic vaccine platform and allows equitable vaccine access to low- and middle-income communities across the globe.

mRNA Technology and Mucosal Immunization

“…This work underscores the value of a mucosal boost vaccination to obtain local and systemic immune responses in previously vaccinated subjects. Second, the nasal administration—without adjuvants—of the ubiquitous and large E. coli bacteriophage T4 was engineered to express the selected virus protein [ 33 ]. Apparently, the sole administration of phage T4 was sufficient to induce a robust cellular and humoral antiviral response in the mucosa of experimental animals.…”