US Army Medical Research Institute of Infectious Diseases, Virology Division, 1425 Porter Street, Fort Detrick, MD 21702, United States.
Vaccine. 2009 Dec 11;28(2):494-511. doi: 10.1016/j.vaccine.2009.09.133. Epub 2009 Oct 13.
Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. 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 (VRPs) 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 x 10(6)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.
自然发生的天花已被成功的疫苗接种运动在 20 世纪 60 年代和 70 年代根除。由于其高度传染性和高死亡率，天花具有作为生物武器的重大潜力。不幸的是，目前的正痘病毒疫苗对很大一部分人群是禁忌的。因此，需要新的、安全和有效的正痘病毒疫苗。源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替代目前的天花疫苗。在这里，我们证明表达痘苗病毒 A33R、B5R、A27L 和 L1R 基因的病毒样复制子颗粒（VRP）在小鼠中引发的保护性免疫与接种活痘苗病毒相当。此外，用四种痘病毒 VRPs（4pox-VRP）组合接种的食蟹猴产生了针对每种抗原的抗体反应。这些抗体反应能够中和并抑制痘苗病毒和猴痘病毒的传播。4pox-VRP、流感 HA VRP（阴性对照）或活痘苗病毒（阳性对照）接种的猕猴在第二次 VRP 接种后 1 个月经静脉内接种 5×10(6)pfu 的猴痘病毒。在六个阴性对照动物中，有四只死于猴痘，其余两只动物表现出严重或严重疾病。重要的是，用 4pox-VRP 疫苗接种的 10 只猕猴均未出现严重疾病而存活。这些发现表明，单次增强 VRP 天花疫苗作为目前许可的活痘苗病毒天花疫苗的安全替代品具有很大的潜力。
