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

• Published in: Annual review of virology Vol. 11; no. 1; pp. 395 - 420
• Main Authors: Zhu, Jingen, Tao, Pan, Chopra, Ashok K, Rao, Venigalla B
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 20-05-2024
• Subjects: bacteriophage T4 assembly; broad humoral immunity; cellular immunity; CRISPR engineering; mucosal immunity; needle- and adjuvant-free intranasal vaccines; pandemic vaccine design
• ISSN: 2327-056X; 2327-0578
• DOI: 10.1146/annurev-virology-111821-111145

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.