Single-dose intranasal administration with mDEF201 (adenovirus vectored mouse interferon-alpha) confers protection from mortality in a lethal SARS-CoV BALB/c mouse model

被引：34

作者：

Kumaki, Yohichi ^{[2
]}

Ennis, Jane ^{[1
]}

Rahbar, Ramtin ^{[1
]}

Turner, Jeffrey D. ^{[1
]}

Wandersee, Miles K. ^{[2
]}

Smith, Aaron J. ^{[2
]}

Bailey, Kevin W. ^{[2
]}

Vest, Zachary G. ^{[2
]}

Madsen, Jason R. ^{[2
]}

Li, Joseph K. -K. ^{[3
]}

Barnard, Dale L. ^{[2
]}

机构：

[1] Defyrus Inc, Toronto, ON M4W 3E2, Canada

[2] Utah State Univ, Inst Antiviral Res, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA

[3] Utah State Univ, Dept Biol, Logan, UT 84322 USA

来源：

ANTIVIRAL RESEARCH | 2011年 / 89卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Interferon; mDEF201; SARS; Treatment; Prophylaxis; ACUTE RESPIRATORY SYNDROME; IN-VITRO; SYNDROME CORONAVIRUS; SPIKE PROTEIN; INFECTION; INHIBITION; VIRUS; REPLICATION; INDUCTION; THERAPY;

D O I：

10.1016/j.antiviral.2010.11.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Interferons (IFNs) are a first line of defense against viral infection. Herein we describe the use of an adenovirus vectored mouse IFN alpha gene (mDEF201) as a prophylactic and treatment countermeasure in a SARS-CoV-infected BALB/c mouse model. Complete survival protection was observed in mice given a single dose of mDEF201 administered intranasally 1, 3, 5, 7, or 14 days prior to lethal SARS-CoV challenge (p < 0.001), and body weights of these treated mice were unaffected by the challenge. In addition, low doses of mDEF201 protected lungs in a dose dependent manner as measured by a reduction in gross pathology. Intranasal treatment with mDEF201 ranging from 10(6) to 10(8) PFU significantly protected mice against a lethal SARS-CoV infection in a dose dependent manner up to 12 h post infection (p < 0.001). The data suggest that mDEF201 is a new class of antiviral agent further development as treatment for SARS-CoV infections. (C) 2010 Elsevier B.V. All rights reserved.

引用

页码：75 / 82

页数：8