PLoS ONE:DNA疫苗聯合鴨蛋防止漢坦病毒疾病
近日,科學家們使用一種新的方法(結合DNA疫苗和>)成功地保護了實驗室動物免於致命的漢坦病毒疾病,研究成果刊登在PLoS ONE雜誌上。
根據美國陸軍醫學研究所傳染病研究所(USAMRIID)研究人員Jay W. Hooper介紹,這是首次證明DNA疫苗/鴨蛋能產生抗病毒藥物來防止漢坦病毒疾病。
>漢坦病毒歸屬布尼亞病毒科,有35-40%的疾病致死率。目前沒有疫苗來預防或治療方法這種高致病性禽流感。
在這項研究中,研究小組使用Andes病毒倉鼠模型,USAMRIID早期的研究表明敘利亞倉鼠會患Andes病毒感染,可以模仿人患疾病的癥狀。
Hooper和他的團隊合作第一次評估了一種天然產品(人多克隆抗體),這是從HPS病人體內獲得新鮮冰凍血漿(FFP)。他們的研究結果表明FFP可以防治HPS疾病。
該研究小組給鴨接種DNA疫苗以抵抗Andes病毒。這種疫苗改造漢坦病毒基因遺傳物質或是DNA編碼以引起系統免疫反應。
接下來,研究人員純化鴨蛋蛋黃抗體IgY。在細胞培養試驗時,此純化後的IgY能夠中和Andes病毒。
研究人員表示:這種抗病毒藥物的產品如果得到充分開發和製造,在未來流感爆發的情況下被使用的話會非常有市場, Hooper說:這種抗病毒藥物產品也可以被用來治療醫護人員和與HPS患者有密切接觸的人。
此外,作者認為由於DNA疫苗/鴨蛋系統的靈活性,可應用於對抗其他傳染性病原體和毒素的抗體的生產。DNA Vaccine-Generated Duck Polyclonal Antibodies as a Postexposure Prophylactic to Prevent Hantavirus Pulmonary Syndrome (HPS)
Rebecca Brocato, Matthew Josleyn, John Ballantyne, Pablo Vial, Jay W. Hooper*
Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35–40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural 「despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the first report demonstrating the in vivo efficacy of any antiviral product produced using DNA vaccine-duck/egg system.
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