Development and preclinical evaluation of an alphavirus replicon vaccine for influenza

被引：59

作者：

Hubby, Bolyn ^{[1
]}

Talarico, Todd ^{[1
]}

Maughan, Maureen ^{[1
]}

Reap, Elizabeth A. ^{[1
]}

Berglund, Peter ^{[1
]}

Kamrud, Kurt I. ^{[1
]}

Copp, Laura ^{[1
]}

Lewis, Whitney ^{[1
]}

Cecil, Chad ^{[1
]}

Norberg, Pamela ^{[1
]}

Wagner, Jordan ^{[1
]}

Watson, Aubrey ^{[1
]}

Negri, Sarah ^{[1
]}

Burnett, Bruce K. ^{[1
]}

Graham, Andrew ^{[1
]}

Smith, Jonathan F. ^{[1
]}

Chulay, Jeffrey D. ^{[1
]}

机构：

[1] AlphaVax Inc, Res Triangle Pk, NC 27709 USA

来源：

VACCINE | 2007年 / 25卷 / 48期

关键词：

influenza vaccine; alphavirus replicon vaccine; cellular immunity;

D O I：

10.1016/j.vaccine.2007.09.038

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We used a propagation-defective, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the hemagglutinin (HA) and neuraminidase (NA) proteins from influenza A/Wyoming/03/2003 (H3N2). Efficient production methods were scaled to produce pilot lots of HA VRP and NA VRP and clinical lots of HA VRP. HA VRP-induced high-titered antibody responses in mice, rabbits and rhesus macaques, as measured by ELISA or hemagglutination inhibition (HI) assays, and robust cellular immune responses in mice and rhesus macaques, as measured by IFN-gamma ELISPOT. NA VRP also induced cellular immune responses in mice. A toxicology study with HA VRP and NA VRP in rabbits showed no adverse effects in any parameter. These studies support clinical testing of alphavirus replicon vaccines for influenza. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：8180 / 8189

页数：10

共 26 条

[1] Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza [J].