Inactivated Hantaan virus vaccine derived from suspension culture of Vero cells

Abstract

We have developed a cell culture-derived, inactivated vaccine against Hantaan virus for prevention of the hemorrhagic fever with renal syndrome (HFRS). Hantaan virus was purified from a microcarrier culture of Vero E6 cells by ultrafiltration and density gradient centrifugation. Viral infection was inactivated by treatment of the viral stock with formaldehyde. Immunogenic properties of the vaccine were characterized in comparison with Hantavax, a mouse brain-derived, formalin-inactivated vaccine that has been in human use for a decade in Korea. Compared to the Hantavax, immunization of Balb/c mice with the cell culture-based vaccine resulted in a moderate difference in antibody response to the viral nucleocapsid protein but more than five-fold increase in neutralizing activity. Moreover, all six mice immunized with 5 microg of the cell culture-based vaccine were fully protected from challenge with infectious virus, whereas virus was detected in lung and spleen of all animals immunized with the same dose of Hantavax. Four times higher dose of the latter vaccine was needed for complete protection. In the analysis of the humoral immune response to the vaccines, we found that all three viral structural proteins, N, G1 and G2 were immunoprecipitated by sera from animals immunized with the cell culture-based vaccine. In contrast, N and some G1 but no G2 were precipitated by the sera from animals immunized with Hantavax. These results suggest that the cell culture-based vaccine can provide more effective immunity than the Hantavax.