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Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.

Abstract The Higgs potentials of extended Higgs sectors exhibit a complex and interesting vacuum structure. When travelling back in time, i.e. going to higher temperatures, the structure may change and exhibit interesting phase patterns and sequences of phases related to the respective minima of the potential. The investigation of the vacuum structure can give us indirect insights in beyond-Standard-Model physics and the evolution of the Universe. In this paper, we investigate the possibility of an intermediate charge-breaking (CB) phase in the 2-Higgs-Doublet Model (2HDM) type I. The existence has been reported previously by using a simple potential setup. We here confirm that the intermediate CB phase can still exist when using the one-loop corrected effective potential including thermal masses. We discuss its features and the relation with SU(2) symmetry (non-)restoration as well as its consistency with the current experimental data. Lastly, we show for some selected benchmark points the rich and interesting phase patterns and sequences that the 2HDM can undergo during its evolution from the early Universe to today’s electroweak vacuum.

The aim of this study is to determine changes in the near-surface layer of ZrO _2 ceramics caused by irradiation with low-energy He ^2+ ions, as well as the associated formation of defects and structural deformations. During the experimental work conducted, it was established that the accumulation of deformation-structural distortions is of two stage nature, having a direct dependence on irradiation fluence and, therefore, on atomic displacement value. It was determined that at small atomic displacement values (less than 10 dpa), the main mechanisms of structural distortions are caused by tensile residual stresses, the value of which is less than 0.1 GPa. At the same time, the deformation distortion of chemical bonds has a pronounced anisotropy associated with a more pronounced distortion of the Zr–O _I chemical bonds, the distortion of which results in the formation of vacancy defects in the form of V _O . During determination of alterations in optical characteristics depending on the atomic displacement value, it was found that the dominant role at small values of dpa (less than 10 dpa) is played by point defects, which influence the formation of obstacles in the form of absorbing centers. In this case, an increase in the irradiation fluence above 10 ^17 ion cm ^−2 results in a growth in the linear refractive index, the change of which has a direct correlation with the value of residual stresses in the damaged layer. Certain dependencies of changes in structural features and their relationship with deformation distortions, as well as the accumulation of vacancy defects, can subsequently be used to predict the potential of using these ceramics as materials for new generation nuclear reactors.