Influence of Individual Mutations in Genes Coding Internal Proteins of the Influenza A Virus on Formation of Humoral and Cellular Immune Response in Mice

This study addresses a current problem of vaccinal prevention—the development of approaches to increase the immunogenicity of influenza vaccines—and it is directed at studying the effect of mutations responsible for the degree of attenuation of influenza viruses on the formation of an immune response. We conducted the analysis of the humoral and cellular immune response in mice with the introduction of strains of the influenza A virus containing single and combined point mutations alike typical for the attenuation donor A/Leningrad/134/17/57 (H2N2), which is used at present for the preparation of domestic live influenza vaccine. In the study, 13 mutant strains were compared to the attenuation donor (containing all these mutations) and its “wild” predecessor (without mutations). It has been shown that the presence in internal genes of the “wild” virus of single mutations that are typical for the attenuation donor, as well as their combinations, can affect not only the quantitative indices of the humoral immune response, but also the rate of accumulation of virus-specific serum and secretory antibodies. A group of viruses with mutations in the M1 gene was isolated based on the ability to stimulate T cell response. A promising approach to development of ways to increase the immunogenic properties of live influenza vaccines will be a further search for a balanced combination of mutations in M1 and NS2 genes that enhance the stimulation of most of the immuneresponse factors studied, with mutations in genes of polymerase complex that impart attenuating properties to strains.