With about 50 structural proteins in the virus, 171-kb of double stranded DNA packaged inside a 120 nm x 86 nm capsid, and a sophisticated tail to deliver its genetic material into Escherichia coli host, bacteriophage T4 is one of the most complex viruses and a fascinating “organism” to study biology.
Bacteriophage nanoparticles can be engineered to deliver vaccine antigens. Pathogen antigens from Bacillus anthracis (anthrax), Yersinia pestis (plague), HIV-1, SARS-CoV-2 (COVID-19) have been arrayed on the virus capsid. Vaccination of mice, rabbits, and rhesus macaques with these particles elicit strong immune responses against the infectious agent, including neutralizing antibodies, T cell, and mucosal responses, and complete protection against lethal challenge. We have integrated CRISPR engineering into the T4-COVID vaccine design to rapidly generate vaccine candidates. Phage T4 allows incorporation of multiple antigens into the same virus nanoparticle that leads to broader immunogenicity and protection. This “universal” vaccine design platform can be applied to any future pandemic pathogen.