Freeman Krista G, Wetzel Katherine S, Zhang Yu, Zack Kira M, Jacobs-Sera Deborah, Walters Sara M, Barbeau Dominique J, McElroy Anita K, Williams John V, Hatfull Graham F
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15260, USA.
Microorganisms. 2021 Nov 23;9(12):2414. doi: 10.3390/microorganisms9122414.
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.
2020年严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的爆发促使疫苗研发及对各种疫苗平台的探索活动激增，其中一些是成熟的平台，一些是新的平台。此前已有基于噬菌体的疫苗的相关描述，我们探索了使用分枝杆菌噬菌体作为展示SARS-CoV-2或其他感染因子抗原的平台的可能性。使用分枝杆菌噬菌体的潜在优势在于，已描述并对大量且多样的此类噬菌体进行了基因组特征分析，有可用的工程工具，并且能够在单个大小约为100纳米的颗粒上展示多达700个抗原拷贝。噬菌体本身可能就是一种良好的佐剂，并且噬菌体易于繁殖，成本低廉，纯度高。此外，这些噬菌体最近在治疗中的应用，包括静脉内给药，表明其具有良好的安全性，尽管疗效可能会受到中和抗体的限制。我们在此描述分枝杆菌噬菌体Bxb1以及展示SARS-CoV-2刺突蛋白抗原的Bxb1重组体的强大免疫原性。
