Development and preclinical evaluation of an alphavirus replicon vaccine for influenza

Vaccine. 2007 Nov 23;25(48):8180-9. doi: 10.1016/j.vaccine.2007.09.038. Epub 2007 Oct 5.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alphavirus / genetics*
  • Animals
  • Antibodies, Viral
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Vectors / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Immunity, Cellular
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Macaca mulatta
  • Mice
  • Neuraminidase / immunology*
  • Rabbits
  • Replicon

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Neuraminidase