Immunization with a recombinant fowlpox virus expressing a hepatitis C virus core-E1 polyprotein variant, protects mice and African green monkeys (Chlorocebus aethiops sabaeus) against challenge with a surrogate vaccinia virus
Immunization with a recombinant fowlpox virus expressing a hepatitis C virus core-E1 polyprotein variant, protects mice and African green monkeys (Chlorocebus aethiops sabaeus) against challenge with a surrogate vaccinia virus
复制标题
DOI：
10.1042/ba20070182
复制
发表时间：
2008-10-01
影响因子：
2.8
通讯作者：
Duenas-Carrera, Santiago
中科院分区：
文献类型：
--
作者：
Alvarez-Lajonchere, Liz;Amador-Canizares, Yalena;Duenas-Carrera, Santiago
HCV（丙型肝炎病毒）是当今世界性的健康问题。目前还没有针对这种病原体的预防性疫苗，目前使用的治疗方法也存在重大缺陷，包括疗效有限。在本工作中，产生了一种表达截断的HCV核心- e1多蛋白的重组禽痘病毒FPCoE1。在BALB/c小鼠中，FPCoE1病毒通常不能引起针对HCV抗原的体液免疫应答。相比之下，在离体ELISPOT（酶联免疫斑点）检测中，接种了FPCoE1的小鼠对HCV核心产生了阳性的干扰素分泌反应。值得注意的是，在用表达HCV结构抗原的重组痘苗病毒vvRE替代攻毒模型中，接种了FPCoE1的小鼠显著地控制了病毒血症。事实上，40%的小鼠卵巢中没有检测到vvRE水平。在黑尾猴（Chlorocebus（原Cercophitecus） aethiops sabaeus）中注射FPCoE1可在50%的免疫动物中诱导针对HCV核心蛋白和E1蛋白的淋巴细胞增殖性反应。接种了FPCoE1的猴子血液中没有检测到vvRE，而接种了阴性对照病毒FP9的猴子在攻击后7天血液中仍有可检测到的vvRE。综上所述，重组鸡痘病毒FPCoE1能够在小鼠和猴子体内诱导抗hcv免疫应答。通过将FPCoE1与其他候选疫苗或抗病毒治疗联合使用，可以合理地利用这种能力来制定对抗HCV感染的有效策略。
HCV (hepatitis C virus) is a worldwide health problem nowadays. No preventive vaccine is available against this pathogen, and therapeutic treatments currently in use have important drawbacks, including limited efficacy. In the present work a recombinant fowlpox virus, FPCoE1, expressing a truncated HCV core-E1 polyprotein, was generated. FPCoE1 virus generally failed to elicit a humoral immune response against HCV antigens in BALB/c mice. By contrast, mice inoculated with FPCoE1 elicited a positive interferon-gamma secretion response against HCV core in ex-vivo ELISPOT (enzyme-linked immunospot) assays. Remarkably, mice inoculated with FPCoE1 significantly controlled viraemia in a surrogate challenge model with vvRE, a recombinant vaccinia virus expressing HCV structural antigens. In fact, 40% of the mice had no detectable levels of vvRE in their ovaries. Administration of FPCoE1 in vervet monkeys [Chlorocebus (formerly Cercophitecus) aethiops sabaeus] induced lymphoproliferative response against HCV core and E1 proteins in 50% of immunized animals. Monkeys immunized with FPCoE1 had no detectable levels of vvRE in their blood, whereas monkeys inoculated with FP9, the negative control virus, had detectable levels of vvRE in blood up to 7 days after challenge. In conclusion, recombinant fowlpox virus FPCoE1 is able to induce an anti-HCV immune response in mice and monkeys. This ability could be rationally employed to develop effective strategies against HCV infection by using FPCoE1 in combination with other vaccine candidates or antiviral treatments.