Adenovirus Serotype 5 Neutralizing Antibodies Target both Hexon and Fiber following Vaccination and Natural Infection

被引：116

作者：

Bradley, Ritu R.

Lynch, Diana M.

Iampietro, Mark J.

Borducchi, Erica N.

Barouch, Dan H. ^{[1
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA

来源：

JOURNAL OF VIROLOGY | 2012年 / 86卷 / 01期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

VECTORS; IMMUNOGENICITY; HUMANS;

D O I：

10.1128/JVI.06254-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：625 / 629

页数：5

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