Validation of cross-genotype neutralization by hepatitis B virus-specific monoclonal antibodies by in vitro and in vivo infection.
Validation of cross-genotype neutralization by hepatitis B virus-specific monoclonal antibodies by in vitro and in vivo infection.
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DOI：
10.1371/journal.pone.0118062
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tanaka Y
中科院分区：
文献类型：
--
作者：
Hamada-Tsutsumi S;Iio E;Watanabe T;Murakami S;Isogawa M;Iijima S;Inoue T;Matsunami K;Tajiri K;Ozawa T;Kishi H;Muraguchi A;Joh T;Tanaka Y
基于 A 基因型乙型肝炎病毒 (HBV) 的疫苗已在全球范围内用于免疫预防，并被认为可以有效预防非 A 型 HBV 病毒株的感染，而 C 基因型疫苗已在多个亚洲国家使用，包括 C 型 HBV 流行的日本和韩国。然而，在日本，由 A 基因型 HBV 感染引起的急性乙型肝炎不断增加，而 C 基因型疫苗针对非 C 型感染的免疫效果知之甚少。我们从接受基于 C 基因型的疫苗免疫的个体中分离出了人单克隆抗体 (mAb)。在本研究中，使用 HBV 感染的体内和体外模型分析了这两种 mAb HB0116 和 HB0478 的功效。将 HBV 基因型 C 静脉接种到具有人类肝细胞的嵌合小鼠中，五周后导致 HBV 感染的建立，而接种物与 HB0116 或 HB0478 预孵育可完全保护嵌合小鼠免受基因型 C 感染。有趣的是，HB0116 和 HB0478 都被发现可以完全阻断 A 基因型感染。此外，乙型肝炎表面蛋白中氨基酸145具有免疫逃逸取代的C基因型菌株的感染也通过与HB0478一起孵育而被完全抑制。最后，剂量依赖性的体外分析表明，完全防止基因型C和基因型A感染所需的HB0478的量分别为5.5 mIU和55 mIU。这些结果表明，基于 C 基因型的疫苗能够诱导针对 HBV 感染的跨基因型免疫。
Vaccines based on hepatitis B virus (HBV) genotype A have been used worldwide for immunoprophylaxis and are thought to prevent infections by non-A HBV strains effectively, whereas, vaccines generated from genotype C have been used in several Asian countries, including Japan and Korea, where HBV genotype C is prevalent. However, acute hepatitis B caused by HBV genotype A infection has been increasing in Japan and little is known about the efficacy of immunization with genotype C-based vaccines against non-C infection. We have isolated human monoclonal antibodies (mAbs) from individuals who were immunized with the genotype C-based vaccine. In this study, the efficacies of these two mAbs, HB0116 and HB0478, were analyzed using in vivo and in vitro models of HBV infection. Intravenous inoculation of HBV genotype C into chimeric mice with human hepatocytes resulted in the establishment of HBV infection after five weeks, whereas preincubation of the inocula with HB0116 or HB0478 protected chimeric mice from genotype C infection completely. Interestingly, both HB0116 and HB0478 were found to block completely genotype A infection. Moreover, infection by a genotype C strain with an immune escape substitution of amino acid 145 in the hepatitis B surface protein was also completely inhibited by incubation with HB0478. Finally, in vitro analysis of dose dependency revealed that the amounts of HB0478 required for complete protection against genotype C and genotype A infection were 5.5 mIU and 55 mIU, respectively. These results suggested that genotype C-based vaccines have ability to induce cross-genotype immunity against HBV infection.
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