日前,PNAS发表了美国亚利桑那大学基础医学科学系研究人员的研究成果。科研人员改造了一种实验性的疫苗,它能够保护小鼠不受埃博拉出血热感染。
在埃博拉病毒首次已知暴发的30年后,这种病毒仍然是致命的,它通过气溶胶、体液和直接接触传播,并且能杀死90%以上的感染者。
Melissa Herbst-Kralovetz及其同事改造了一种埃博拉免疫复合体,它是由在这种病毒的表面发现的一种蛋白质的一部分与识别这种病毒蛋白的抗体结合起来组成的,然后他们在烟草植株中制造了这种复合体。这组作者然后在小鼠皮下注射了一种由两部份组成的疫苗——分别是来自植物的这种免疫复合体以及一种称为PIC的免疫调控化学物质,后者能激活一种参与到先天性免疫的生物化学的级联反应。当实验性地用扎伊尔埃博拉病毒感染小鼠的时候,超过80%的用这种疫苗预先治疗过的小鼠从感染中生存了下来。相比之下,注射不含PIC的这种免疫复合体的小鼠死于了这种病毒。
此前制造埃博拉疫苗的尝试没能产生能够在国家减少生物威胁储备库中长期储存而保持稳定的疫苗。这组作者说,在烟草植株中有成本效益地制造这种埃博拉免疫复合体有可能帮助克服这种缺陷并产生稳定的疫苗。(生物谷Bioon.com)
doi:10.1073/pnas.1117715108
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A nonreplicating subunit vaccine protects mice against lethal Ebola virus challenge
Waranyoo Phoolcharoen, John M. Dye, Jacquelyn Kilbourne, Khanrat Piensook, William D. Pratt, Charles J. Arntzen, Qiang Chen, Hugh S. Mason, and Melissa M. Herbst-Kralovetz
Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen–antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD50 of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.