Development and preclinical evaluation of an alphavirus replicon vaccine for influenza

Development and preclinical evaluation of an alphavirus replicon vaccine for influenza
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DOI:
10.1016/j.vaccine.2007.09.038
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发表时间:
2007-11-23
期刊:
影响因子:
5.5
通讯作者:
Chulay, Jeffrey D.
Chulay, Jeffrey D.
中科院分区:
医学3区
文献类型:
--
作者:
Hubby, Bolyn;Talarico, Todd;Chulay, Jeffrey D.

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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.