Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10970510 | Vaccine | 2007 | 10 Pages |
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-γ 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
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Immunology
Authors
Bolyn Hubby, Todd Talarico, Maureen Maughan, Elizabeth A. Reap, Peter Berglund, Kurt I. Kamrud, Laura Copp, Whitney Lewis, Chad Cecil, Pamela Norberg, Jordan Wagner, Aubrey Watson, Sarah Negri, Bruce K. Burnett, Andrew Graham, Jonathan F. Smith,