Biology subjects

Zubkova, O. V.

Publications and source records attributed to Zubkova, O. V..

4 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2024

Seroprevalence and cross-reactivity of neutralizing antibodies to six types of adenoviruses

BackgroundThe use of adenoviral vector vaccines is an effective way to induce an antiviral immune response. Most vaccines used worldwide are based on human adenovirus type 5 (Ad5). Pre-existing natural immunity to Ad5 is a limitation to the frequent use of Ad5-based vectors in gene therapy and vaccination. In the present study, we assessed the seroprevalence and cross-reactivity of neutralizing antibodies to six adenovirus types: Ad1, Ad2, Ad5, Ad19, Ad26, and Ad37. MethodsThe study used immunological and virological research methods. Adenovirus vectors encoding the enhanced green fluorescent protein (EGFP) were developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology. For seroprevalence and cross-neutralation study we used a panel of sera from 101 volunteers. ResultsThe conducted correlation analysis showed a strong relationship between seropositivity and the geometric mean titer of neutralizing antibodies to adenovirus. An increase in antibody titers indicates the formation of a humoral immune response and population immunity. We determined that there is no cross-reactivity between NtAbs to Ad1, Ad2, Ad5 and Ad26. ConclusionsBased on the presented data, we assume that Ad1 or Ad2 should be considered the most promising alternative candidates for the development of vaccine vectors.

immunology↗

bioRxiv2024

Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during inflammation

The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells that is particularly prevalent on endothelial cells lining the vasculature. It has been hypothesized that the glycocalyx mediates leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including the chronic skin disease, psoriasis. Here, we show that leukocytes express heparan sulfate, an important glycocalyx component, on their cell surface which is lost in response to psoriasis-like skin inflammation, whilst endothelial heparan sulfate expression is not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation protected heparan sulfate from cleavage by heparanase and resulted in reduced leukocyte accumulation in skin, yet unexpectedly, led to increased clinical signs of inflammation due to reduced Treg numbers. These findings reshape our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context. One Sentence SummaryLeukocytes express a glycocalyx on their surface which is shed in response to psoriasis-like skin inflammation, facilitating their migration into the skin.

immunology↗

bioRxiv2021

Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern

Virus-neutralizing antibodies are one of the few treatment options for COVID-19. The evolution of SARS-CoV-2 virus has led to the emergence of virus variants with reduced sensitivity to some antibody-based therapies. The development of potent antibodies with a broad spectrum of neutralizing activity is urgently needed. Here we isolated a panel of single-domain antibodies that specifically bind to the receptor-binding domain of SARS-CoV-2 S glycoprotein. Three of the selected antibodies exhibiting most robust neutralization potency were used to generate dimeric molecules. We observed that these modifications resulted in up to a 200-fold increase in neutralizing activity. The most potent heterodimeric molecule efficiently neutralized each of SARS-CoV-2 variant of concern, including Alpha, Beta, Gamma, Delta and Omicron variants. This heterodimeric molecule could be a promising drug candidate for a treatment for COVID-19 caused by virus variants of concern.

immunology↗