[Needle-Free Jet-Delivered mRNA-Vaccine Encoding Influenza A(H1N1)pdm09 Hemagglutinin Protects Mice from Lethal Virus Infection].

Abstract

Seasonal influenza is an acute respiratory illness caused by the influenza A and B viruses that circulate worldwide. Due to high variability, new strains of the virus emerge every year. Therefore, vaccine formulation has to be revised every year. The advantages of mRNA vaccines are that they can be produced quickly and without preliminary adaptation of the vaccine strain to chicken embryos. Here, the results of developing and studying the mRNA-C3-H1 vaccine encoding the hemagglutinin (HA) of the influenza A(H1N1)pdm09 virus are presented. The design and production of a DNA-template for the synthesis of mature HA mRNA in one step were described. The obtained mRNA was purified from double-stranded RNA impurities using a method based on the use of cellulose powder. The efficacy of the vaccine was assessed on BALB/c mice. The mice were immunized with a "naked" mRNA vaccine using a needle-free jet injector. According to the ELISA results, the average antibody titer in the serum of immunized animals was 4.6 x 10^(5). Sera of immunized animals neutralized the mouse-adapted influenza A/California/04/09 (H1N1) MA8 virus with an average titer of 6 x 10^(2). As shown by the ELISpot method, the developed mRNA vaccine induced a T-cell immune response in mice. After stimulation of splenocytes with specific peptides, the average number of T-lymphocytes secreting IFN-γ was 236 per 10^(6) cells. Immunization with the mRNA vaccine was shown to protect mice from infection with a lethal dose of the influenza A/California/04/09 (H1N1) MA8 virus. Thus, the developed experimental mRNA-C3-H1 vaccine is immunogenic and prevents morbidity and mortality in mice after infection with a homologous strain of the influenza virus.