The development of a vaccine against influenza caused by highly pathogenic avian influenza (HPAI) viruses of the A/H5 subtype is a pressing issue due to concerns about the pandemic potential of this subtype. It is evident that mRNA vaccines possess a multitude of characteristics that are indispensable for the development of an influenza vaccine. In general, lipid nanoparticles (LNPs) are utilized for the delivery of exogenous mRNA into the cells of the body. Additionally, the needle-free jet injection (JI) method has emerged as a promising alternative to LNPs for mRNA delivery.

An experimental mRNA vaccine encoding a modified hemagglutinin (HA) trimer of the H5N8 influenza virus has been obtained. The HA gene was subsequently cloned into the pVAX-Cas1CC expression cassette, which carries the target gene under the control of the T7 promoter. The cassette also contains 5'- and 3'-untranslated regions of human α-globin and 100-nucleotide poly-(A)-tail. The mRNA was encapsulated in LNPs. Subsequently, BALB/c mice were immunized with mRNA delivered by LNPs and as "naked" mRNA by JI. The control groups consist of naïve mice, mice that have been immunized with a recombinant protein and LNPs without mRNA.

Studies have shown that mice, immunized with obtained mRNA delivered by LNPs and JI, can effectively stimulate humoral and T-cell immune responses. A comparative evaluation showed that mRNA-LNPs exhibited the highest levels of humoral immune response stimulation, while JI stimulated an immune response at lower levels that were nevertheless sufficient to protect animals from lethal infection with both homologous and heterologous H5Nx viruses. The data indicate that mRNA-H5 is a promising influenza vaccine candidate against the HPAI virus subtype A/H5 with pandemic potential.

This study was conducted by the Federal State Budgetary Institution State Research Center Vector of Rospotrebnadzor as part of a state assignment.