Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox

Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox
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DOI:
10.1128/jvi.78.9.4433-4443.2004
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发表时间:
2004-05-01
影响因子:
5.4
通讯作者:
Jahrling, PB
Jahrling, PB
中科院分区:
医学2区
文献类型:
--
作者:
Hooper, JW;Thompson, E;Jahrling, PB

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在全球疫苗接种运动成功根除自然发生的天花20年后,生物恐怖主义的威胁导致了新的疫苗接种计划。此外,非洲零星爆发的人类猴痘和最近在美国爆发的人类猴痘清楚地表明,自然发生的人畜共患正痘病毒疾病仍然是一个公共卫生问题。正痘病毒造成的大部分威胁可以通过接种疫苗消除;然而,由于天花疫苗是一种施用于皮肤的活正痘病毒疫苗(牛痘病毒),疫苗本身可能造成严重的健康风险。在这里,我们证明了恒河猴接种了含有四种牛痘病毒基因(L1R、A27L、A33R和B5R)的DNA疫苗后,在受到猴痘病毒的致命攻击后,可以免受严重疾病的侵害。接种了编码中和抗体靶标的单基因(L1R)疫苗的动物出现了严重的疾病,但存活了下来。这是首次证明亚单位疫苗方法对天花-猴痘免疫是可行的。
Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.