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Shidlovskaya, E. V.

Publications and source records attributed to Shidlovskaya, E. V..

3 recordsLinked to original sources

Comparison candidate Tick-borne encephalitis virus vaccines based on mRNA, adenovirus serotype 25 and chimera of YFV vaccine strain

BackgroundDespite the availability of several licensed inactivated vaccines, the development of new vaccines against the Tick-borne encephalitis virus (TBEV) remains an important task, especially in countries endemic to this pathogen. The risk of infection with TBEV increases every year because of increase in the number of ticks, the emergence of tick carriers into new territories, and active human activity in areas of TBEV natural foci. Annual reports of vaccination failures have prompted us to search for approaches to creating a new vaccine. ObjectivesIn our study, we used the same PrM and E antigens to produce three vaccine candidates against tick-borne encephalitis (TBE): 1) a live attenuated YFV 17DD-UN vaccine strain, 2) recombinant adenovirus (rAd) vectors, and 3) mRNA encapsulated in lipid nanoparticles (LNP). MethodsWe generated and assessed the immunogenicity and protective efficacy of three candidate TBEV vaccines based on mRNA, simian adenovirus type 25, and a chimera of the YFV 17DD-UN attenuated strain. ResultsAnalysis of the virus-neutralizing titers in the blood sera of immunized mice revealed a statistically significant difference among the three candidate vaccines. The immunogenicity and protective efficacy of the candidate mRNA-LNP vaccine were found to be higher than those of the other two vaccines. ConclusionsBased on the results of our study, it can be concluded that the mRNA-based platform is more promising for the creation of a vaccine against TBEV.

immunology↗

Major role of S-glycoprotein in providing immunogenicity and protective immunity in mRNA lipid nanoparticle vaccines based on SARS-CoV-2 structural proteins

Recently we have developed an mRNA lipid nanoparticle (mRNA-LNP) platform providing efficient long-term expression of an encoded gene in vivo after both intramuscular and intravenous application. Based on this platform, we have generated mRNA-LNP coding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combinations in vivo. As a result, all candidate vaccine compositions coding S and N proteins induced excellent anti-RBD and N titers of binding antibodies. T cell responses mainly represented specific CD4+ T cell lymphocyte producing IL-2 and TNF-. mRNA-LNP coding M protein did not show high immunogenicity. High neutralizing activity was detected in sera of mice vaccinated with mRNA-LNP coding S protein (alone or in combinations) against closely related strains but was not detectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to the mRNA-N in the vaccine composition enhanced immunogenicity of mRNA-N inducing more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancement of immune response to the N protein in the mRNA-LNP vaccine.

immunology↗

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

ABSTRACTSeasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. It also imposes a substantial economic burden through increased absenteeism during periods of active pathogen circulation. Vaccination is generally accepted as the most effective strategy for influenza prevention. As both influenza A and B viruses circulate and cause seasonal epidemics, vaccines need to include multiple antigens derived from different viral subtypes. 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 candidates, evaluate its immunogenicity using the hemagglutination inhibition assay, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidates 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.

immunology↗