Pichla-Gollon Susan L, Lin Shih-Wen, Hensley Scott E, Lasaro Marcio O, Herkenhoff-Haut Larissa, Drinker Mark, Tatsis Nia, Gao Guang-Ping, Wilson James M, Ertl Hildegund C J, Bergelson Jeffrey M
Division of Infectious Diseases, the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
J Virol. 2009 Jun;83(11):5567-73. doi: 10.1128/JVI.00405-09. Epub 2009 Mar 11.
A major obstacle to the use of adenovirus vectors derived from common human serotypes, such as human adenovirus 5 (AdHu5), is the high prevalence of virus-neutralizing antibodies in the human population. We previously constructed a variant of chimpanzee adenovirus 68 (AdC68) that maintained the fundamental properties of the carrier but was serologically distinct from AdC68 and resisted neutralization by AdC68 antibodies. In the present study, we tested whether this modified vector, termed AdCDQ, could induce transgene product-specific CD8(+) T cells in mice with preexisting neutralizing antibody to wild-type AdC68. Contrary to our expectation, the data show conclusively that antibodies that fail to neutralize the AdCDQ mutant vector in vitro nevertheless impair the vector's capacity to transduce cells and to stimulate a transgene product-specific CD8(+) T-cell response in vivo. The results thus suggest that in vitro neutralization assays may not reliably predict the effects of virus-specific antibodies on adenovirus vectors in vivo.
使用源自常见人类血清型的腺病毒载体（如人腺病毒5型，AdHu5）的一个主要障碍是人类群体中病毒中和抗体的高流行率。我们之前构建了黑猩猩腺病毒68型（AdC68）的一个变体，该变体保留了载体的基本特性，但在血清学上与AdC68不同，并且能抵抗AdC68抗体的中和作用。在本研究中，我们测试了这种被称为AdCDQ的修饰载体能否在预先存在针对野生型AdC68的中和抗体的小鼠中诱导转基因产物特异性CD8(+) T细胞。与我们的预期相反，数据确凿地表明，那些在体外不能中和AdCDQ突变载体的抗体，在体内却会损害该载体转导细胞以及刺激转基因产物特异性CD8(+) T细胞反应的能力。因此，这些结果表明体外中和试验可能无法可靠地预测病毒特异性抗体对体内腺病毒载体的影响。
