Investigation of Efficiency of Site-Specific Mutants of the Influenza Virus in Homological and Heterological Control Infection

The immunogenicity and protective efficacy of the site-specific mutants of A/WSN/33 (H1N1) strain of the influenza virus were compared with the similar characteristics of the cold-adapted (CA) reassortant obtained by crossing A/WSN/33 strain and CA A/ Krasnodar/101/35/59 (H2N2) strain of the influenza virus under homologous and heterologous control infection. The site-specific mutants had ts-mutations localized in the genes encoding the proteins of the polymerase complex. Groups of mice were immunized intranasally with site-specific mutants and CA reassortant and then infected with specific doses of A/WSN/33 strain and A/Duck. Pennsylvania/10218/84 (H5N2) strain of avian influenza virus adapted to mice. The titer of antibodies inhibiting haemagglutination was higher in mice immunized with site-specific mutants than in mice immunized with CA-reassortant. With homologous control infection, an effective suppression of the propagation of the A/WSN/33 virulent strain was observed in the lungs of mice immunized with both one and the other vaccine preparation. In case of heterologous control of mice entering the control group, the H5N2 strain of the avian influenza virus was 78 ± 6.5% lethality. In the group of mice immunized with CA-reassortant 35 ± 4.2% mortality was observed. In mice immunized with site-specific mutants (transfectants No. 2 and No. 5), 100% survival was noted. In the group of mice immunized with transfectant No. 8 after the control heterologous infection, lethality reached 16 ± 3.0%. The data obtained indicate that the site-specific mutants of the influenza virus are not inferior to the investigated useful characteristics of CA with reassortant influenza vaccines and can be used as live influenza vaccines.