Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential.

We generated a high-growth 7:1 reassortant (Len17/H5) that contained the hemagglutinin (HA) gene from non-pathogenic A/Duck/Potsdam/1402-6/86 (H5N2) virus and other genes from the cold-adapted (ca) attenuated A/Leningrad/134/17/57 (H2H2) strain. Len17/H5 demonstrated an attenuated phenotype in mice and did not infect chickens. Mice administered Len17/H5 either as a live-attenuated intranasal vaccine or as an inactivated intramuscular vaccine were substantially protected from lethal challenge with highly pathogenic A/Hong Kong/483/97 (H5N1) virus and were protected from pulmonary infection with antigenically distinct A/Hong Kong/213/2003 (H5N1) virus. The cross-protective effect correlated with the levels of virus-specific mucosal IgA and/or serum IgG antibodies. Our results suggest a new strategy of using classical genetic reassortment between a high-growth ca H2N2 strain and antigenically related non-pathogenic avian viruses to prepare live-attenuated and inactivated vaccines for influenza pandemic.

Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents.

The immunogenicity and efficacy of Russian live attenuated and US inactivated trivalent influenza vaccines administered alone or in three different combinations were evaluated in a randomized, placebo-controlled, double-blinded study of 614 elderly or chronically ill nursing home residents in St. Petersburg, Russia during the 1996-97 influenza season. Postvaccination serum antibody responses were more frequent among individuals administered the combination vaccines than among those vaccinated with live or inactivated vaccine alone. Only individuals who received live vaccine, alone or in combination with inactivated vaccine, achieved significant postvaccination increases in virus-specific nasal IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These results suggest that administration of a combination of influenza vaccines may provide a strategy for improved influenza vaccination of elderly people.