Development of MDCK-based quadrivalent split seasonal influenza virus vaccine with high safety and immunoprotection: A preclinical study

Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response

“…When immunogenicity was analyzed by ELISA method (against H1N1pdm) for the group of mice immunized with the combined mRNA vaccine, as well as in our case, 10-100 times higher levels of antibodies (depending on the dose of mRNA) were observed compared to this value in the group of animals vaccinated with quadrivalent inactivated vaccine (at a dose of 1.5 µg). The levels of antibody response for the inactivated vaccine obtained in our experiments were in good agreement with the data of the cell-based split vaccine study [35]. For a 1.5 μg dose of each antigen separately, HAI titers comparable to those obtained in our work for the quadrivalent vaccine were obtained (HAI titers to H1N1 averaged about 1:90, to H3N2 averaged about 1:500, and to B (Victoria lineage) averaged about 1:30).…”

“…These data correlated with the dynamics of weight of infected animals (for split vaccine, weight loss was observed from days 3 to 9 of observation), as well as viral load in the lungs - on day 3, the difference in viral load between the groups that received mRNA composition and split vaccine was 10 6 . We were unable to find studies that examined the protectiveness of mRNA and split vaccines in a single animal experiment, but there are studies of split vaccine candidates produced by virus production in the MDCK cell line [35]. On day 4 after 10 7 CCID 50 infection with H1N1 influenza virus, a weight loss of up to 10% was observed in the group of mice vaccinated with 5 μg split mono-vaccine, and the amount of virus in the lungs of infected mice isolated on day 6 was 10 2 virus copies/mL, compared with 10 5 virus copies/mL in the placebo group.…”

Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response

“…These data correlated with the dynamics of weight of infected animals (for split vaccine, weight loss was observed from days 3 to 9 of observation), as well as viral load in the lungs - on day 3, the difference in viral load between the groups that received mRNA composition and split vaccine was 10 6 . We were unable to find studies that examined the protectiveness of mRNA and split vaccines in a single animal experiment, but there are studies of split vaccine candidates produced by virus production in the MDCK cell line ( 41 ). On day 4 after 10 7 cell culture infectious dose 50% (CCID 50 ) infection with H1N1 influenza virus, a weight loss of up to 10% was observed in the group of mice vaccinated with 5 μg split mono-vaccine, and the amount of virus in the lungs of infected mice isolated on day 6 was 10 2 virus copies/mL, compared with 10 5 virus copies/mL in the placebo group.…”

The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity

“…In this study, we identified a new strategy to enhance the yield of cell-based influenza vaccines. Existing strategies for increasing influenza virus production are primarily based on identifying new cell lines with high susceptibility [ 8 , 38 ] or modifying the host MDCK cell line [ 7 , 9 , 10 , 39 ]. In contrast to these approaches, we focused on modifying the viral culture media to enable broader vaccine production applications.…”

“…However, several problems remain unresolved, such as the high cost and low yield of egg-based vaccines [ 7 ]. Numerous attempts have been made to establish a system for producing high-yield influenza vaccines, including the development of novel modified cell lines to improve influenza virus [ 8 - 10 ]. For example, Hamamoto et al .…”