Development and preclinical evaluation of an alphavirus replicon vaccine for influenza |
| |
Authors: | Hubby Bolyn Talarico Todd Maughan Maureen Reap Elizabeth A Berglund Peter Kamrud Kurt I Copp Laura Lewis Whitney Cecil Chad Norberg Pamela Wagner Jordan Watson Aubrey Negri Sarah Burnett Bruce K Graham Andrew Smith Jonathan F Chulay Jeffrey D |
| |
Institution: | AlphaVax, Inc., 2 Triangle Drive, Research Triangle Park, NC 27709, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|