Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Abstract

The rapid spread and the transmission to humans of avian influenza virus (H5N1) have induced world-wide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but also against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.

Fig. 1

The level of IFN-γ (a) and IL-4 (b) spot-forming cells (SFC)/10⁶ in spleens of Balb/c mice as determined by ELISPOT assay. Mice were immunized as described in the text either with 1.5μg hemagglutinin of inactivated whole virus vaccines (VN1203, IN5/05 or B/JS) or recombinant H5 vaccine (rH5-HA, derived from VN1203). Splenocytes were stimulated in-vitro with 0.1μg/mL hemagglutinin of inactivated whole influenza viruses or rH5-HA (stim. antigens) as shown in the insert of the upper panel. Bars represent means ±SD of spot counts in quadruplicate wells.