Someya Kenji, Xin Ke-Qin, Ami Yasushi, Izumi Yasuyuki, Mizuguchi Hiroyuki, Ohta Shinrai, Yamamoto Naoki, Honda Mitsuo, Okuda Kenji
Department of Virology III, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
Virology. 2007 Oct 25;367(2):390-7. doi: 10.1016/j.virol.2007.06.012. Epub 2007 Jul 12.
Replication-defective adenovirus type 5 (Ad5) vector-based vaccines are widely known to induce strong immunity against immunodeficiency viruses. To exploit this immunogenicity while overcoming the potential problem of preexisting immunity against human adenoviruses type 5, we developed a recombinant chimeric adenovirus type 5 with type 35 fiber vector (rAd5/35). We initially produced a simian immunodeficiency virus (SIV) gag DNA plasmid (rDNA-Gag), a human immunodeficiency virus type 1 (HIV-1) 89.6 env DNA plasmid (rDNA-Env) and a recombinant Ad5/35 vector encoding the SIV gag and HIV env gene (rAd5/35-Gag and rAd5/35-Env). Prime-boost vaccination with rDNA-Gag and -Env followed by high doses of rAd5/35-Gag and -Env elicited higher levels of cellular immune responses than did rDNAs or rAd5/35s alone. When challenged with a pathogenic simian human immunodeficiency virus (SHIV), animals receiving a prime-boost regimen or rAd5/35s alone maintained a higher number of CD4(+) T cells and remarkably suppressed plasma viral RNA loads. These findings suggest the clinical promise of an rAd5/35 vector-based vaccine.
众所周知，基于复制缺陷型5型腺病毒（Ad5）载体的疫苗可诱导针对免疫缺陷病毒的强大免疫力。为了利用这种免疫原性，同时克服针对5型人类腺病毒的预先存在的免疫可能带来的问题，我们开发了一种带有35型纤维载体的重组嵌合5型腺病毒（rAd5/35）。我们最初制备了猿猴免疫缺陷病毒（SIV）gag DNA质粒（rDNA-Gag）、1型人类免疫缺陷病毒（HIV-1）89.6 env DNA质粒（rDNA-Env）以及编码SIV gag和HIV env基因的重组Ad5/35载体（rAd5/35-Gag和rAd5/35-Env）。先用rDNA-Gag和-Env进行初免-加强免疫，随后给予高剂量的rAd5/35-Gag和-Env，与单独使用rDNAs或rAd5/35相比，可引发更高水平的细胞免疫反应。当用致病性猿猴-人类免疫缺陷病毒（SHIV）进行攻击时，接受初免-加强免疫方案或单独使用rAd5/35的动物维持了更多数量的CD4(+) T细胞，并显著抑制了血浆病毒RNA载量。这些发现表明基于rAd5/35载体的疫苗具有临床应用前景。
