日前,PNAS發(fā)表了美國亞利桑那大學基礎(chǔ)醫(yī)學科學系研究人員的研究成果,??蒲腥藛T改造了一種實驗性的疫苗,,它能夠保護小鼠不受埃博拉出血熱感染。
在埃博拉病毒首次已知暴發(fā)的30年后,,這種病毒仍然是致命的,,它通過氣溶膠、體液和直接接觸傳播,,并且能殺死90%以上的感染者,。
Melissa Herbst-Kralovetz及其同事改造了一種埃博拉免疫復合體,它是由在這種病毒的表面發(fā)現(xiàn)的一種蛋白質(zhì)的一部分與識別這種病毒蛋白的抗體結(jié)合起來組成的,,然后他們在煙草植株中制造了這種復合體,。這組作者然后在小鼠皮下注射了一種由兩部份組成的疫苗——分別是來自植物的這種免疫復合體以及一種稱為PIC的免疫調(diào)控化學物質(zhì),后者能激活一種參與到先天性免疫的生物化學的級聯(lián)反應,。當實驗性地用扎伊爾埃博拉病毒感染小鼠的時候,,超過80%的用這種疫苗預先治療過的小鼠從感染中生存了下來。相比之下,,注射不含PIC的這種免疫復合體的小鼠死于了這種病毒,。
此前制造埃博拉疫苗的嘗試沒能產(chǎn)生能夠在國家減少生物威脅儲備庫中長期儲存而保持穩(wěn)定的疫苗。這組作者說,,在煙草植株中有成本效益地制造這種埃博拉免疫復合體有可能幫助克服這種缺陷并產(chǎn)生穩(wěn)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.