Centre for Cell Factories and Biopolymers (CCFB), Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia.
National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, PR China.
ACS Infect Dis. 2022 Apr 8;8(4):744-756. doi: 10.1021/acsinfecdis.1c00434. Epub 2022 Mar 3.
is an opportunistic human pathogen that is intrinsically resistant to multiple antibiotics, causing severe and persistent infections in immunocompromised individuals. This bacterium has been listed as a priority pathogen by the WHO in 2017, and there is no vaccine available for human use. In this study, 10 vaccine candidate antigens were selected for particulate vaccine design. We engineered to assemble biopolymer particles (BPs) that were either coated with epitopes (Ag) derived from OprF/I-AlgE proteins or PopB or PopB-Ag or coated with single or double copies of epitopes (10Ag and 10Ag(2x)) derived from OprF, OprI, AlgE, OprL, PopB, PilA, PilO, FliC, Hcp1, and CdrA. Antigen-coated BPs showed a diameter of 0.93-1.16 μm with negative surface charge. Antigens attached to BPs were identified by mass spectrometry. Vaccination with BP-Ag, BP-PopB, BP-PopBAg, PB-10Ag, and BP-10Ag(2x) with and without Alhydrogel adjuvant induced significant antigen-specific humoral and cell-mediated immune responses in mice. All particulate vaccines with Alhydrogel induced protection in an acute pneumonia murine model of infection, contributing to up to 80% survival when administered intramuscularly, and the addition of Alhydrogel boosted immunity. The BP-10Ag(2x) vaccine candidate showed the best performance and even induced protective immunity in the absence of Alhydrogel. Intramuscular administration of the BP-10Ag(2x) without Alhydrogel vaccine resulted in 60% survival. Intranasal vaccination induced immunity, contributing to about 90% survival. Overall, our data suggest that vaccination with BPs coated with antigens induce protective immunity against infections. The possibility of intranasal delivery will strongly facilitate administration and use of BP vaccines.
是一种机会性的人体病原体，对多种抗生素具有内在抗性，导致免疫功能低下的个体发生严重和持续的感染。该细菌于 2017 年被世界卫生组织列为优先病原体，目前尚无供人类使用的疫苗。在本研究中，选择了 10 种疫苗候选抗原用于颗粒疫苗设计。我们设计了 将生物聚合物颗粒（BP）组装在一起，这些颗粒要么涂有源自 OprF/I-AlgE 蛋白或 PopB 或 PopB-Ag 的表位（Ag），要么涂有源自 OprF、OprI、AlgE、OprL、PopB、PilA、PilO、FliC、Hcp1 和 CdrA 的单个或两个拷贝的表位（10Ag 和 10Ag(2x))。Ag 涂层的 BP 显示出 0.93-1.16μm 的直径，带有负表面电荷。通过质谱鉴定了附着在 BP 上的抗原。用 BP-Ag、BP-PopB、BP-PopBAg、PB-10Ag 和 BP-10Ag(2x) 以及不加或加 Alhydrogel 佐剂对小鼠进行免疫接种，可诱导显著的抗原特异性体液和细胞介导免疫反应。所有含有 Alhydrogel 的颗粒疫苗均可在 感染的急性肺炎小鼠模型中提供保护，当肌肉内给药时，可高达 80%的存活率，并且添加 Alhydrogel 可增强免疫力。BP-10Ag(2x) 疫苗候选物表现最佳，甚至在没有 Alhydrogel 的情况下也能诱导保护性免疫。不含 Alhydrogel 的 BP-10Ag(2x) 疫苗的肌肉内给药导致 60%的存活率。鼻内接种可诱导免疫，约 90%的存活率。总体而言，我们的数据表明，用涂有 抗原的 BP 进行免疫接种可诱导针对 感染的保护性免疫。鼻内给药的可能性将极大地促进 BP 疫苗的管理和使用。
