Development and preclinical evaluation of an alphavirus replicon vaccine for influenza.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hubby, B; Talarico, T; Maughan, M; Reap, EA; Berglund, P; Kamrud, KI; Copp, L; Lewis, W; Cecil, C; Norberg, P; Wagner, J; Watson, A; Negri, S; Burnett, BK; Graham, A; Smith, JF; Chulay, JD

Published Date

  • November 2007

Published In

Volume / Issue

  • 25 / 48

Start / End Page

  • 8180 - 8189

PubMed ID

  • 17961878

Pubmed Central ID

  • 17961878

Electronic International Standard Serial Number (EISSN)

  • 1873-2518

International Standard Serial Number (ISSN)

  • 0264-410X

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2007.09.038


  • eng