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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees
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Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees

机译：接种丙型肝炎病毒样颗粒可控制黑猩猩感染丙型肝炎病毒

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摘要

Recombinant hepatitis C virus (HCV)-like particles (HCV-LPs) containing HCV structural proteins (core, E1, and E2) produced in insect ceils resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice and baboons. Here, we present evidence on the immunogenicity and induction of protective immunity by HCV-LPs in chimpanzees. Chimpanzees (two in each group), were immunized with HCV-LPs or HCV-LPs plus AS01B adjuvant. After immunizations, all animals developed an HCV-specific immune response including IFN-γ~+, IL-2~+, CD4~+, and CD8~+ T cell and proliferative lymphocyte responses against core, E1, and E2. Upon challenge with an infectious HCV inoculum, one chimpanzee developed transient viremia with low HCV RNA titers (10~3 to 10~4 copies per ml) in the third and fourth weeks after the challenge. The three other chimpanzees became infected with higher levels of viremia (10~4 to 10~5 copies per ml), but their viral levels became unquantifiable ( < 10~3 copies per ml) 10 weeks after the challenge. After the HCV challenge, all four chimpanzees demonstrated a significant increase in peripheral and intrahepatic T cell and proliferative responses against the HCV structural proteins. These T cell responses coincided with the fall in HCV RNA levels. Four naieve chimpanzees were infected with the same HCV inoculum, and three developed persistent infection with higher viremia in the range of 10~5 to 10~6 copies per ml. Our study suggests that HCV-LP immunization induces HCV-specific cellular immune responses that can control HCV challenge in the chimpanzee model.
机译：在昆虫细胞中产生的包含丙型肝炎病毒结构蛋白（核心，E1和E2）的重组丙型肝炎病毒（HCV）样颗粒（HCV-LPs）与推定的HCV病毒粒子相似，能够在体内诱导强烈而广泛的体液和细胞免疫应答老鼠和狒狒。在这里，我们提供了关于黑猩猩中HCV-LPs的免疫原性和保护性免疫诱导的证据。用HCV-LP或HCV-LP加AS01B佐剂免疫黑猩猩（每组两只）。免疫后，所有动物均产生HCV特异性免疫反应，包括IFN-γ〜+，IL-2〜+，CD4〜+和CD8〜+ T细胞以及针对核心，E1和E2的增殖淋巴细胞反应。用感染性HCV接种物攻击后，一只黑猩猩在攻击后的第三和第四周发展出了短暂的病毒血症，HCV RNA滴度低（每毫升10〜3至10〜4拷贝）。攻击后十周，其他三只黑猩猩感染了更高水平的病毒血症（每毫升10〜4至10〜5份），但其病毒水平无法量化（每毫升<10〜3份）。 HCV攻击后，所有四只黑猩猩均表现出外周和肝内T细胞的显着增加以及针对HCV结构蛋白的增殖反应。这些T细胞反应与HCV RNA水平下降同时发生。四只幼稚的黑猩猩感染了相同的HCV接种物，三只发生了持续感染，病毒血症的发生率更高，每毫升10〜5至10〜6份。我们的研究表明，HCV-LP免疫可以诱导HCV特异性细胞免疫反应，从而可以控制黑猩猩模型中的HCV攻击。

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