携带HIV gp41表位2F5的嵌合甲型肝炎病毒（HAV）的免疫原性

Immunogenicity of a chimeric hepatitis A virus (HAV) carrying the HIV gp41 epitope 2F5.

作者信息

Kusov Yuri Y, Zamjatina Natalja A, Poleschuk Valentina F, Michailov Michail I, Morace Graziella, Eberle Josef, Gauss-Müller Verena

机构信息

Institute of Medical Molecular Biology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.

出版信息

Antiviral Res. 2007 Feb;73(2):101-11. doi: 10.1016/j.antiviral.2006.08.003. Epub 2006 Sep 5.

DOI:10.1016/j.antiviral.2006.08.003

PMID:17014915

Abstract

Its stable particle structure combined with its high immunogenicity makes the hepatitis A virus (HAV) a perfect carrier to expose foreign epitopes to the host immune system. In an earlier report [Beneduce, F., Kusov, Y., Klinger, M., Gauss-Müller, V., Morace, G., 2002. Chimeric hepatitis A virus particles presenting a foreign epitope (HIV gp41) at their surface. Antiviral Res. 55, 369-377] chimeric virus-like particles (HAV-gp41) were described that carried at their surface the dominant gp41 epitope 2F5 (2F5e) of the human immunodeficiency virus HIV-1. Extending this work, we now report that chimeric virus HAV-gp41 replicates in HAV-susceptible cells as well as in non-human primates. Infected marmosets developed both an anti-HAV and anti-2F5 epitope immune response. Furthermore, an HIV-neutralizing antibody response was elicited in guinea pigs immunized with HAV-gp41 chimeric particles. The results demonstrate that the replication-competent chimeric HAV-gp41 can serve as either a live or a subunit vaccine for eliciting of antibodies directed against a foreign antigenic epitope.

摘要

甲型肝炎病毒（HAV）稳定的颗粒结构及其高免疫原性使其成为向宿主免疫系统呈现外源表位的理想载体。在较早的一份报告中[贝内杜切，F.，库索夫，Y.，克林格，M.，高斯 - 米勒，V.，莫拉切，G.，2002年。在其表面呈现外源表位（HIV gp41）的嵌合甲型肝炎病毒颗粒。抗病毒研究。55，369 - 377]描述了嵌合病毒样颗粒（HAV - gp41），其在表面携带人类免疫缺陷病毒HIV - 1的显性gp41表位2F5（2F5e）。扩展这项工作，我们现在报告嵌合病毒HAV - gp41在对HAV敏感的细胞以及非人类灵长类动物中都能复制。受感染的狨猴产生了抗HAV和抗2F5表位的免疫反应。此外，在用HAV - gp41嵌合颗粒免疫的豚鼠中引发了HIV中和抗体反应。结果表明，具有复制能力的嵌合HAV - gp41可作为活疫苗或亚单位疫苗，用于引发针对外源抗原表位的抗体。