Román-Cruz Valery C, Miller Shannon M, Schoener Roman A, Lukasiewicz Chase, Schmidt Amelia K, DeBuysscher Blair L, Burkhart David, Secor Patrick R, Evans Jay T
Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
Center for Translational Medicine, University of Montana, Missoula, MT 59812, USA.
Vaccines (Basel). 2024 Jan 24;12(2):115. doi: 10.3390/vaccines12020115.
(), a WHO priority 1 pathogen, resulted in approximately 559,000 deaths globally in 2019. has a multitude of host-immune evasion strategies that enhance virulence. Most clinical isolates of are infected by a phage called Pf that has the ability to misdirect the host-immune response and provide structural integrity to biofilms. Previous studies demonstrate that vaccination against the coat protein (CoaB) of Pf4 virions can assist in the clearance of from the dorsal wound model in mice. Here, a consensus peptide was derived from CoaB and conjugated to cross-reacting material 197 (CRM197). This conjugate was adjuvanted with a novel synthetic Toll-like receptor agonist (TLR) 4 agonist, INI-2002, and used to vaccinate mice. Mice vaccinated with CoaB-CRM conjugate and INI-2002 developed high anti-CoaB peptide-specific IgG antibody titers. Direct binding of the peptide-specific antibodies to whole-phage virus particles was demonstrated by ELISA. Furthermore, a functional assay demonstrated that antibodies generated from vaccinated mice disrupted the replicative cycle of Pf phages. The use of an adjuvanted phage vaccine targeting is an innovative vaccine strategy with the potential to become a new tool targeting multi-drug-resistant infections in high-risk populations.
（）是世界卫生组织重点关注的1类病原体，2019年在全球导致约55.9万人死亡。（）具有多种宿主免疫逃避策略，可增强其毒力。大多数（）临床分离株都感染了一种名为Pf的噬菌体，该噬菌体能够误导宿主免疫反应并为生物膜提供结构完整性。先前的研究表明，针对Pf4病毒粒子的外壳蛋白（CoaB）进行疫苗接种有助于清除小鼠背部伤口模型中的（）。在此，从CoaB衍生出一种共有肽，并将其与交叉反应物质197（CRM197）偶联。这种偶联物与一种新型合成Toll样受体激动剂（TLR）4激动剂INI-2002一起用作佐剂，用于给小鼠接种疫苗。用CoaB-CRM偶联物和INI-2002接种疫苗的小鼠产生了高抗CoaB肽特异性IgG抗体滴度。通过ELISA证明了肽特异性抗体与全噬菌体病毒颗粒的直接结合。此外，一项功能试验表明，接种疫苗的小鼠产生的抗体破坏了Pf噬菌体的复制周期。使用针对（）的佐剂噬菌体疫苗是一种创新的疫苗策略，有可能成为针对高危人群中多重耐药（）感染的新工具。
