Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates
Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates
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DOI：
10.1093/infdis/jix180
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发表时间：
2017-06-15
影响因子：
6.4
通讯作者：
Huang, Zhong
中科院分区：
文献类型：
--
作者：
Li, Dapeng;Wang, Xuesong;Huang, Zhong
背景由于新的直接作用抗病毒药物（DAA）的价格高昂和潜在的耐药性，以及DAA治愈患者再次感染的风险，全球丙型肝炎病毒（HCV）感染的控制仍然是一个巨大的负担。因此，HCV的预防性疫苗非常重要。我们以前报道过，在昆虫细胞中产生的单一重组可溶性E2（sE 2）疫苗能够诱导广泛中和抗体（NAbs），并防止小鼠HCV感染。在此，在非人灵长类动物中评价了sE 2疫苗。用sE 2疫苗与不同佐剂联合免疫恒河猴。在抗血清中检测疫苗诱导的NAb对一组细胞培养衍生的HCV（HCV-HCV）的中和活性，同时在脾细胞、外周血单核细胞和肝淋巴细胞中评价T细胞应答。在恒河猴中，sE 2能够引发针对来自多种HCV基因型的携带HCV结构蛋白的HCV的NAb。此外，sE 2免疫的猕猴开发系统和肝内记忆T细胞特异性E2。sE 2特异性免疫球蛋白G滴度与中和谱之间存在显著相关性，强调了sE 2免疫原性在获得广泛NAb方面的重要作用。sE 2是一种有前途的HCV疫苗候选物，值得进一步的临床前和临床开发。
Background. The global control of hepatitis C virus (HCV) infection remains a great burden, owing to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs), as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported that a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice. Here the sE2 vaccine was evaluated in non-human primates.Methods. Rhesus macaques were immunized with sE2 vaccine in combination with different adjuvants. Vaccine-induced NAbs in antisera were tested for neutralization activities against a panel of cell culture-derived HCV (HCVcc), while T-cell responses were evaluated in splenocytes, peripheral blood mononuclear cells, and hepatic lymphocytes.Results. sE2 is able to elicit NAbs against HCVcc harboring structural proteins from multiple HCV genotypes in rhesus macaques. Moreover, sE2-immunized macaques developed systemic and intrahepatic memory T cells specific for E2. A significant correlation between the sE2-specific immunoglobulin G titers and neutralization spectrum was observed, highlighting the essential role of sE2 immunogenicity on achieving broad NAbs.Conclusions. sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.