Biryukov Sergei S, Cote Christopher K, Klimko Christopher P, Dankmeyer Jennifer L, Rill Nathaniel O, Shoe Jennifer L, Hunter Melissa, Shamsuddin Zain, Velez Ivan, Hedrick Zander M, Rosario-Acevedo Raysa, Talyansky Yuli, Schmidt Lindsey K, Orne Caitlyn E, Fetterer David P, Burtnick Mary N, Brett Paul J, Welkos Susan L, DeShazer David
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United States.
Department of Microbiology and Immunology, University of Nevada, Reno School of Medicine, Reno, NV, United States.
Front Microbiol. 2022 Aug 17;13:965518. doi: 10.3389/fmicb.2022.965518. eCollection 2022.
and the closely related species, , produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three vaccine candidates against lethal aerosol challenges with K96243, MSHR5855, and FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live 668 Δ strain, provided significant protection and were down-selected for further investigation and advanced development.
与之密切相关的物种，……，会引发类似的多方面疾病，这些疾病从迅速致命到迁延慢性不等，并且是流行地区死亡的主要原因。除了引起自然感染外，这两种微生物都是一级潜在生物威胁因子。抗生素治疗时间长且效果不一，因此迫切需要有效的疫苗。我们研究的目的是比较针对类鼻疽和鼻疽的候选疫苗，以确定最有效的疫苗，并确定将其过渡到非人灵长类动物气溶胶模型的剩余要求。在C57BL/6小鼠模型中进行研究，以评估三种候选疫苗针对用K96243、MSHR5855和FMH进行致死性气溶胶攻击的体液免疫和细胞介导免疫反应以及保护效力。重组疫苗对疫苗抗原产生了显著的免疫反应，减毒活疫苗对OPS和整个细菌细胞产生了更强的免疫反应。无论评估哪种候选疫苗，小鼠的保护都与暴露于雾化细菌后肺内细胞因子反应减弱有关。尽管通过两种不同的平台递送并产生了不同的免疫反应，但两种实验性疫苗，即荚膜结合物+Hcp1亚单位疫苗和减毒活668Δ菌株，提供了显著的保护，并被选定进行进一步研究和推进开发。
