Efficacy of H5 Influenza Vaccines Produced by Reverse Genetics in a Lethal Mouse Model

We studied the efficacy, in mice, of 2 H5 influenza vaccine viruses produced by reverse genetics. Mice were immunized with inactivated viruses and then inoculated with a human H5N1 1997 or 2003 virus or an avian H5N1 2001 virus. Vaccine viruses that we tested raised high levels of hemagglutination-inhibiting (1:160-1:1280) and virus-neutralizing (1:900-1:1900) antibodies on day 21 after a single dose of vaccine and decreased or prevented virus replication in mouse lungs; 54.5%-100% of immunized mice survived, whereas all control mice died. Protection was achieved despite antigenic differences and incomplete matching of the vaccine strain and the challenge virus. Therefore, high levels of cross-protection are predicted in the mouse model.