Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
J Virol. 2012 Jan;86(1):625-9. doi: 10.1128/JVI.06254-11. Epub 2011 Nov 9.
The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). However, the role of NAbs directed against other capsid components, particularly the adenovirus fiber, remains unclear. Here we show that Ad5 NAbs target both hexon and fiber following vaccination and natural infection. Utilizing neutralization assays with capsid chimeric vectors, we observed that NAb responses to hexon appeared dominant and NAb responses against fiber were subdominant in sera from vaccinated mice, vaccinated humans, and naturally exposed humans. A novel chimeric Ad5 vector in which both the hexon HVRs and the fiber knob were exchanged nearly completely evaded Ad5-specific NAbs both in vitro and in vivo.
腺病毒血清型 5（Ad5）载体的免疫原性已被证明受到主要针对六邻体超变区（HVR）的中和抗体（NAb）的抑制。然而，针对其他衣壳成分（特别是腺病毒纤维）的 NAb 的作用仍不清楚。在这里，我们表明接种疫苗和自然感染后，Ad5 NAb 会靶向六邻体和纤维。利用衣壳嵌合载体的中和测定，我们观察到针对六邻体的 NAb 反应似乎占主导地位，而针对纤维的 NAb 反应在疫苗接种小鼠、疫苗接种人类和自然暴露人类的血清中则处于次要地位。一种新型嵌合 Ad5 载体，其中六邻体 HVR 和纤维扣均几乎完全交换，在体外和体内均能逃避 Ad5 特异性 NAb。
