Development and preclinical evaluation of an alphavirus replicon vaccine for influenza.
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.
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Related Subject Headings
- Virology
- Replicon
- Rabbits
- Neuraminidase
- Mice
- Macaca mulatta
- Influenza Vaccines
- Influenza A Virus, H3N2 Subtype
- Immunity, Cellular
- Hemagglutinin Glycoproteins, Influenza Virus
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virology
- Replicon
- Rabbits
- Neuraminidase
- Mice
- Macaca mulatta
- Influenza Vaccines
- Influenza A Virus, H3N2 Subtype
- Immunity, Cellular
- Hemagglutinin Glycoproteins, Influenza Virus