Combined Adenovirus Vector and Hepatitis C Virus Envelope Protein Prime-Boost Regimen Elicits T Cell and Neutralizing Antibody Immune Responses
Combined Adenovirus Vector and Hepatitis C Virus Envelope Protein Prime-Boost Regimen Elicits T Cell and Neutralizing Antibody Immune Responses
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DOI：
10.1128/jvi.03574-13
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Folgori, Antonella
中科院分区：
文献类型：
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作者：
Chmielewska, Alicja M.;Naddeo, Mariarosaria;Folgori, Antonella
尽管最近在开发新的抗病毒药物方面取得了进展，但丙型肝炎病毒（HCV）感染仍然是一个主要的全球卫生问题，因此需要一种预防性疫苗。我们之前报道过，表达HCV非结构蛋白的腺病毒载体在黑猩猩中引起保护性T细胞反应，在健康志愿者中具有免疫原性。此外，用佐剂MF59配制的重组HCV E1E2蛋白在黑猩猩中诱导了保护性抗体反应，并在人类中具有免疫原性。为了开发一种能够诱导T细胞和抗体反应的HCV疫苗，我们构建了表达全长和截断的HCV基因型1b的E1E2包膜糖蛋白的腺病毒载体。用腺病毒和重组E1E2糖蛋白（基因型1a）加MF59的异源免疫方案在小鼠和豚鼠中进行了评价。腺病毒引物和蛋白增强诱导广泛的hcv特异性CD8（+）和CD4(+) T细胞反应和功能性th1型IgG反应。免疫血清中和了表达HCV包膜糖蛋白（HCVpp）和多种重组细胞培养衍生的HCV （HCVcc）菌株的荧光素酶报告伪颗粒，限制了HCV在细胞间的传播。本研究表明，腺病毒载体与蛋白抗原结合可诱导较强的抗体和T细胞反应，超过单独接种任一疫苗所获得的免疫反应。
Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8(+) and CD4(+) T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to- cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone.