Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.
Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.
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DOI：
10.1016/j.vaccine.2009.09.133
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发表时间：
2009-12-11
期刊：
影响因子：
5.5
通讯作者：
Kamrud KI
中科院分区：
文献类型：
--
作者：
Hooper JW;Ferro AM;Golden JW;Silvera P;Dudek J;Alterson K;Custer M;Rivers B;Morris J;Owens G;Smith JF;Kamrud KI
由于在1960年代和1970年代成功开展了疫苗接种运动，自然发生的天花被根除。由于其高度传染性和高死亡率，天花具有作为生物武器的巨大潜力。不幸的是，目前的正痘病毒疫苗对大部分人群是禁忌的。因此，需要新的、安全的和有效的正痘病毒疫苗。来自委内瑞拉马脑炎病毒株的甲病毒复制子载体正被用于开发目前天花疫苗的替代品。在这里，我们证明了表达牛痘病毒A33 R，B5 R，A27 L和L1 R基因的病毒样复制子颗粒（VRP）在小鼠中引起的保护性免疫力与活牛痘病毒疫苗接种相当。此外，用四种痘病毒VRP（4pox-VRP）的组合接种的食蟹猴产生了对每种抗原的抗体应答。这些抗体反应能够中和和抑制牛痘病毒和猴痘病毒的传播。在第二次VRP接种后1个月，用5 × 106 PFU猴痘病毒静脉内攻毒接种了4pox-VRP、流感HA VRP（阴性对照）或活牛痘病毒（阳性对照）的猕猴。6只阴性对照动物中有4只死于猴痘，其余2只动物表现出重度或严重疾病。重要的是，所有10只接种4pox-VRP疫苗的猕猴都存活下来，没有发生严重的疾病。这些研究结果表明，一个单一的加强VRP天花疫苗显示出作为一个安全的替代目前许可的活牛痘病毒天花疫苗的希望。
Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine.
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影响因子：
5.5
作者：
Golden, Joseph W.;Josleyn, Matthew D.;Hooper, Jay W.
通讯作者：
Hooper, Jay W.
影响因子：
6.4
作者：
BURKE, DS;RAMSBURG, HH;EDELMAN, R
通讯作者：
EDELMAN, R
影响因子：
5.4
作者：
Aldaz-Carroll, L;Whitbeck, JC;Cohen, GH
通讯作者：
Cohen, GH
影响因子：
5.4
作者：
Fogg, C;Lustig, S;Moss, B
通讯作者：
Moss, B
影响因子：
3.7
作者：
Bernard, KA;Klimstra, WB;Johnston, RE
通讯作者：
Johnston, RE