Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Stamira D'Ancona 20, 20127 Milan, Italy.
Virology. 2012;431(1-2):1-11. doi: 10.1016/j.virol.2012.05.005. Epub 2012 Jun 2.
Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of two different regions, corresponding to the leucine zipper motif in the HR1 alpha-helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This study aimed at reproducing such protective responses through VLP vaccination. Six regions covering the alpha-helical regions of gp41 were conjugated to the surface of AP205 phage-based VLPs. Once administered in mice via systemic or mucosal route, these immunogens elicited high titers of gp41-specific IgG. Immunogenicity and HIV infectivity reduction were obtained either with HR2 regions or with peptides where aminoacid strings were added to either the C-terminus or N-terminus of core epitope in HR1 region. Antibody-dependent cell cytotoxicity (ADCC) activity was induced by one of the HR2 epitopes only. These results may have relevant implications for the development of new vaccinal approaches against HIV infection.
天然针对 gp41 的抗体通过识别两个不同的区域来抑制 HIV-1 的复制，这两个区域分别对应 HR1 螺旋的亮氨酸拉链基序和 HR2 区域内的另一个基序，该基序包含 2F5 和 4E10 表位。本研究旨在通过 VLP 疫苗接种来重现这种保护性反应。将六个覆盖 gp41 的 α-螺旋区域的区域与基于 AP205 噬菌体的 VLPs 表面缀合。通过全身或粘膜途径在小鼠中给药后，这些免疫原引发了针对 gp41 的高滴度 IgG。通过 HR2 区域或通过在 HR1 区域的核心表位的 C 末端或 N 末端添加氨基酸序列，获得了免疫原性和 HIV 感染性降低。仅 HR2 表位之一可诱导抗体依赖性细胞毒性 (ADCC) 活性。这些结果可能对开发针对 HIV 感染的新疫苗接种方法具有重要意义。
