Abstract
The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size. The phage body may itself be a good adjuvant, and the phages can be propagated easily, cheaply, and to high purity. Furthermore, the recent use of these phages therapeutically, including by intravenous administration, suggests an excellent safety profile, although efficacy can be restricted by neutralizing antibodies. We describe here the potent immunogenicity of mycobacteriophage Bxb1, and Bxb1 recombinants displaying SARS-CoV-2 Spike protein antigens.
Highlights
All of the mycobacteriophages described to date are doublestranded DNA (dsDNA)-tailed phages with genomes ranging from 40–160 kbp
The specific role of these extensions is not known, but we note that this general relationship is seen with some other mycobacteriophages (e.g., Wildcat) where the extensions contain Ig-like motifs, as described for many other phages [44,45]
We show that mycobacteriophages such as Bxb1 and its derivatives can be genetically manipulated, and we have advanced our understanding of the opportunities and limitations of peptide display on the capsid subunits
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Bacteriophage-based vaccine systems have been explored using a variety of specific platforms, but none are yet in routine clinical use in humans [1]. The COVID-19 pandemic illustrates the need for flexibility in vaccine development, and the potential roles of platforms such as those based on mRNA, adenovirus systems, and nanoparticles have been explored [2]. Continued exploration of phage-based systems offers the potential for new low cost, high production vaccines, and the global pandemic of SARS-CoV-2 provides a context for such development
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