Airway basal cells from human-induced pluripotent stem cells: a new frontier in cystic fibrosis research.

Human-induced airway basal cells (hiBCs) derived from human-induced pluripotent stem cells (hiPSCs) offer a promising cell model for studying lung diseases, regenerative medicine, and developing new gene therapy methods. We analyzed existing differentiation protocols and proposed our own protocol for obtaining hiBCs, which involves step-by-step differentiation of hiPSCs into definitive endoderm, anterior foregut endoderm, NKX2.1+ lung progenitors, and cultivation on basal cell medium with subsequent cell sorting using the surface marker CD271 (NGFR). We derived hiBCs from two healthy cell lines and three cell lines with cystic fibrosis (CF). The obtained hiBCs, expressing basal cell markers (NGFR, KRT5, and TP63), could differentiate into lung organoids (LOs). We demonstrated that LOs derived from hiBCs can assess cystic fibrosis transmembrane conductance regulator (CFTR) channel function using the forskolin-induced swelling (FIS) assay. We also carried out non-viral (electroporation) and viral (recombinant adeno-associated virus (rAAV)) serotypes 6 and 9 and recombinant adenovirus (rAdV) serotype 5 transgene delivery to hiBCs and showed that rAAV serotype 6 is most effective against hiBCs, potentially applicable for gene therapy research.

Analysis of environmental factors influencing lumpy skin disease outbreak seasonality and assessment of its spread risk in the Saratovskaya oblast of Russia.

Background and Aim: Lumpy skin disease (LSD) is a transboundary viral disease of cattle that causes serious economic losses due to a significant decrease in meat and milk productivity. This study analyzed the influence of natural and anthropogenic environmental factors on LSD spread seasonality and assessed the risk of LSD outbreaks in the Saratovskaya oblast of the Russian Federation. Materials and Methods: Data on LSD outbreaks and environmental factors during different seasons were collected for the period 2011-2020 in the Balkan Peninsula, Middle East, and Russia. Risk assessment was performed using mathematical modeling with generalized linear regression and maximum entropy. Results: Fourteen statistically significant environmental factors influencing LSD spread were identified. The analysis of MaxEnt models built using the selected factors showed that the presence of the pathogen is mostly exerted by: the density of susceptible cattle (an increased risk is observed at a density above 10 and 20 heads/10 km2 in winter and autumn, with a permanent risk in spring and summer), the density of water bodies (the risk is increased at any density in winter and autumn, in the range of 13-23.5 m2/km2 in spring, in the ranges of 0-8 and over 14.5 m2/km2 in summer), and average monthly precipitation rate (the most risky are 105-185 mm/month in winter, 35 mm in spring, 15-105 mm in summer, and above 50 mm in autumn). Conclusion: LSD tends to spread during the warm season. Compared with other test zones, the Saratovskaya oblast has a negligible risk of disease spread (in winter), low risk (in spring), or medium risk (in summer and autumn). The annual risk is low to medium.

NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins.

Increased recruitment of transitional and non-classical monocytes in the lung during SARS-CoV-2 infection is associated with COVID-19 severity. However, whether specific innate sensors mediate the activation or differentiation of monocytes in response to different SARS-CoV-2 proteins remain poorly characterized. Here, we show that SARS-CoV-2 Spike 1 but not nucleoprotein induce differentiation of monocytes into transitional or non-classical subsets from both peripheral blood and COVID-19 bronchoalveolar lavage samples in a NFκB-dependent manner, but this process does not require inflammasome activation. However, NLRP3 and NLRC4 differentially regulated CD86 expression in monocytes in response to Spike 1 and Nucleoprotein, respectively. Moreover, monocytes exposed to Spike 1 induce significantly higher proportions of Th1 and Th17 CD4 + T cells. In contrast, monocytes exposed to Nucleoprotein reduce the degranulation of CD8 + T cells from severe COVID-19 patients. Our study provides insights in the differential impact of innate sensors in regulating monocytes in response to different SARS-CoV-2 proteins, which might be useful to better understand COVID-19 immunopathology and identify therapeutic targets.

Glycemic Control in Patients Living With HIV Initiated on Integrase Inhibitor-Based Three-Drug Antiretroviral Therapy.

Background: The increased risk of cardio-metabolic disorders associated with people living with human immunodeficiency virus (HIV) is of growing importance. Given the broad adoption of integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as first-line therapy for HIV, additional data are needed regarding the metabolic effects of these regimens. Objective: The purpose of this study is to assess glycemic control in patients started on INSTI-based 3-drug regimens over a 2-year period. Methods: A retrospective study was conducted on patients seen in the Brooklyn Hospital Center. Men and nonpregnant, nonlactating women aged 18 years or older with a diagnosis of HIV who were initiated on or switched to an ART consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an INSTI were included in the analysis. The primary endpoint is change in A1C from baseline (pre-INSTI initiation) to 2 years after initiation. Results: Two hundred fifty-one patients were eligible based on specified inclusion and exclusion criteria. Overall, a statistically significant increase in A1C was seen in all patients started on INSTI-based regimen (95% CI, 0.10-0.36; P < 0.001). Primarily patients on both elvitegravir-based and bictegravir-based regimens saw the most significant increase in A1C: 0.16% (95% CI, 0.04-0.27; P = 0.006) and 0.39% (95% CI, 0.02-0.76; P = 0.038), respectively. Conclusion and Relevance: Integrase strand-transfer inhibitor-based 3-drug ART was associated with a small but statistically significant increase in A1C over a 2-year period, requiring additional monitoring by clinicians.

Narrativization of human population genetics: Two cases in Iceland and Russia.

Using the two cases of the Icelandic Health Sector Database and Russian initiatives in biobanking, the article criticizes the view of narratives and imaginaries as a sufficient and unproblematic means of shaping public understanding of genetics and justifying population-wide projects. Narrative representations of national biobanking engage particular imaginaries that are not bound by the universal normative framework of human rights, promote affective thinking, distract the public from recognizing and discussing tangible ethical and socioeconomic issues, and harm trust in science and technology. In the Icelandic case, the presentation of the project in association with national imaginaries concealed its market identity and could lead to the commodification of biodata. In the Russian case, framing in terms of "genetic sovereignty" and "civilizational code" offers pretexts for state securitization. Adherence to normative framework of human rights and public discussion of genetics in an argumentative and factual mode can counter these trends.

MICa/b-dependent activation of natural killer cells by CD64+ inflammatory type 2 dendritic cells contributes to autoimmunity.

Primary Sjögren's syndrome (pSS) is an inflammatory autoimmune disorder largely mediated by type I and II interferon (IFN). The potential contribution of innate immune cells, such as natural killer (NK) cells and dendritic cells (DC), to the pSS pathology remains understudied. Here, we identified an enriched CD16+ CD56hi NK cell subset associated with higher cytotoxic function, as well as elevated proportions of inflammatory CD64+ conventional dendritic cell (cDC2) subtype that expresses increased levels of MICa/b, the ligand for the activating receptor NKG2D, in pSS individuals. Circulating cDC2 from pSS patients efficiently induced activation of cytotoxic NK cells ex vivo and were found in proximity to CD56+ NK cells in salivary glands (SG) from pSS patients. Interestingly, transcriptional activation of IFN signatures associated with the RIG-I/DDX60 pathway, IFN I receptor, and its target genes regulate the expression of NKG2D ligands on cDC2 from pSS patients. Finally, increased proportions of CD64hi RAE-1+ cDC2 and NKG2D+ CD11b+ CD27+ NK cells were present in vivo in the SG after poly I:C injection. Our study provides novel insight into the contribution and interplay of NK and cDC2 in pSS pathology and identifies new potential therapy targets.

Influence of Extracellular Matrix Components on the Differentiation of Periodontal Ligament Stem Cells in Collagen I Hydrogel.

Regeneration of periodontal tissues requires an integrated approach to the restoration of the periodontal ligament, cementum, and alveolar bone surrounding the teeth. Current strategies in endogenous regenerative dentistry widely use biomaterials, in particular the decellularized extracellular matrix (dECM), to facilitate the recruitment of populations of resident cells into damaged tissues and stimulate their proliferation and differentiation. The purpose of our study was to evaluate the effect of the exogenous components of the extracellular matrix (hyaluronic acid, laminin, fibronectin) on the differentiation of periodontal ligament stem cells (PDLSCs) cultured with dECM (combinations of decellularized tooth matrices and periodontal ligament) in a 3D collagen I hydrogel. The immunohistochemical expression of various markers in PDLSCs was assessed quantitatively and semi-quantitatively on paraffin sections. The results showed that PDLSCs cultured under these conditions for 14 days exhibited phenotypic characteristics consistent with osteoblast-like and odontoblast-like cells. This potential has been demonstrated by the expression of osteogenic differentiation markers (OC, OPN, ALP) and odontogenic markers (DSPP). This phenomenon corresponds to the in vivo state of the periodontal ligament, in which cells at the interface between bone and cementum tend to differentiate into osteoblasts or cementoblasts. The addition of fibronectin to the dECM most effectively induces the differentiation of PDLSCs into osteoblast-like and odontoblast-like cells under 3D culture conditions. Therefore, this bioengineered construct has a high potential for future use in periodontal tissue regeneration.

Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study.

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost "Sputnik V" vaccine administered at 1/10 and 1/5 doses to adolescents aged 12-17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants. Clinical Trial Registration: ClinicalTrials.gov, NCT04954092, LP-007632.

On the relationship between the properties of planar structures of non-ionic surfactants and their vesicular analogues - Niosomes.

In recent years, the study of niosomes as nanocarriers alternative to liposomes has received increasing attention. In contrast to well-studied liposome membranes, many aspects of the behavior of analogous niosome bilayers have not been studied. This paper considers one of these aspects related to the communication between the physicochemical properties of planar and vesicular objects. We present the first results of comparative studies of Langmuir monolayers of binary and ternary (with cholesterol) mixtures of non-ionic surfactants based on sorbitan esters and niosomal structures assembled from the same materials. The Thin-Film Hydration (TFH) method in the gentle shaking version was used to produce the particles of large sizes, while small unilamellar high quality vesicles with a unimodal distribution of particles were prepared by TFH using ultrasonic treatment and extrusion. An analysis of the structural organization and phase state of monolayers based on compression isotherms and supplemented by thermodynamic calculations, as well as the results of determining the particle morphology, polarity and microviscosity of niosome shells, made it possible to obtain fundamental data on the intermolecular interactions of the components and their packing in shells and to relate these data to the properties of niosomes. This relationship can be used to optimize the composition of niosome membranes and predict the behavior of these vesicular systems. It was shown that cholesterol excess creates regions of bilayers with increased rigidity (like "lipid rafts"), which hinders the process of folding film fragments into small niosomes.

Decellularized Matrix Induced Spontaneous Odontogenic and Osteogenic Differentiation in Periodontal Cells.

The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells.

Pancreatic ductal adenocarcinoma: tumor microenvironment and problems in the development of novel therapeutic strategies.

Diagnosis and treatment of carcinoma of the exocrine part of the pancreas is a serious problem for modern medicine. Despite the identification of a large number of aberrant mutations in pancreatic ductal adenocarcinoma (PDAC), attempts to create effective therapeutic agents based on identified genetic or epigenetic variations have not been succesful. The role of the tumor microenvironment (TME) in tumor progression is currently a popular topic. Cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) are the main components of the tumor stroma and play an important role in the proliferation, invasiveness and metastasis of cancer. However, the mechanisms underlying the effect of CAFs and ECM on cancer progression are still unclear. Recent studies on stromal components and blockage of signaling pathways have brought some optimism to this area. New information on the role of TME will lead to the development of targeted therapies or combinations with modern chemotherapy for PDAC.

Cross-Reactive Fc-Fused Single-Domain Antibodies to Hemagglutinin Stem Region Protect Mice from Group 1 Influenza a Virus Infection.

The continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which bind to the stem domain of hemagglutinin and efficiently neutralize H1N1 and H5N2 influenza viruses in vivo. In this study, we modified these VHHs with Fc-fragment to enhance their antiviral activity. Reformatting of G2.3 into bivalent Fc-fusion molecule increased its in vitro neutralizing activity against H1N1 and H2N3 viruses up to 80-fold and, moreover, resulted in obtaining the ability to neutralize H5N2 and H9N2 subtypes. We demonstrated that a dose as low as 0.6 mg/kg of G2.3-Fc or H1.2-Fc administered systemically or locally before infection could protect mice from lethal challenges with both H1N1 and H5N2 viruses. Furthermore, G2.3-Fc reduced the lung viral load to an undetectable level. Both VHH-Fc antibodies showed in vivo therapeutic efficacy when delivered via systemic or local route. The findings support G2.3-Fc as a potential therapeutic agent for both prophylaxis and therapy of Group 1 influenza A infection.

Distribution of Order Parameter in Solids under High Pressure Torsion.

Severe plastic deformation (SPD) can lead to various phase transformations. High-pressure torsion (HPT) is one of the most important variants of SPD. In principle, HPT can continue almost indefinitely long, as long as the plungers are not destroyed. However, the number of defects in a material during HPT deformation cannot increase indefinitely. When the rate of defects production becomes equal to the rate of their annihilation, a steady state or dynamic equilibrium is reached. Unexplored is the issue of establishing equilibrium at the initial stage of plunger torsion, when there is an angular acceleration. The parameters of the steady state are described here using the idea of an order parameter in solids in the framework of Landau phenomenological theory and the Landau-Khalatnikov equation.

NLRC4-mediated activation of CD1c+ DC contributes to perpetuation of synovitis in rheumatoid arthritis.

The individual contribution of specific myeloid subsets such as CD1c+ conventional DC (cDC) to perpetuation of rheumatoid arthritis (RA) pathology remains unclear. In addition, the specific innate sensors driving pathogenic activation of CD1c+ cDC in patients with RA and their functional implications have not been characterized. Here, we assessed phenotypical, transcriptional, and functional characteristics of CD1c+ and CD141+ cDC and monocytes from the blood and synovial fluid of patients with RA. Increased levels of CCR2 and the IgG receptor CD64 on circulating CD1c+ cDC was associated with the presence of this DC subset in the synovial membrane in patients with RA. Moreover, synovial CD1c+ cDC are characterized by increased expression of proinflammatory cytokines and high abilities to induce pathogenic IFN-γ+IL-17+CD4+ T cells in vitro. Finally, we identified the crosstalk between Fcγ receptors and NLRC4 as a potential molecular mechanism mediating pathogenic activation, CD64 upregulation, and functional specialization of CD1c+ cDC in response to dsDNA-IgG in patients with RA.

Analysis of peste des petits ruminants virus spread and the risk of its introduction into the territory of the Russian Federation.

Aim: This study examines methods to effectively control peste des petits ruminants (PPR), an emerging, highly contagious, transboundary disease that has been designated as a highly dangerous disease by the World Organization for Animal Health. Mathematical modeling was used as a predictive and preventive tool to assess the risk of PPR virus spread in the model area and the probability of its introduction into the territory of the Russian Federation. Materials and Methods: PPR risk assessment was performed by modeling the pathogen's ecological niche by performing linear regression analysis in the geographic information system ESRI ArcGIS Desktop and maximum entropy methods using MaxEnt software. The territories of Bangladesh, China, and Algeria were used as model countries because they have the highest number of confirmed PPR outbreaks, as reported by the Food and Agriculture Organization of the United Nations from 2009 to 2020. The prepared global model of the PPR pathogen's ecological niche was extrapolated onto the territory of the Far Eastern regions of the Russian Federation to assess the probability of virus introduction in that region. Results: Global model analysis showed that two factors exerted the highest influence on the spread of the PPR pathogen on a global scale: The minimum temperature of the coldest month of the year and the density of roads per unit area, which reflect the overall economic activity within a region. The highest risk of PPR spread was observed in areas with a minimum annual temperature of 16°C and road density of 5000 m/km2 . Conclusion: According to the model, areas with a dominant subtropical climate, where small livestock breeding is performed and where the average daily air temperature is >0°C throughout the year, are at the highest risk of PPR outbreaks. The risk of PPR spreading outside these areas is significantly reduced. Local extrapolation of the PPR ecological niche model demonstrates that the probability of epizootic development does not exceed 3-4% within the territories of the constituent entities of the Russian Federation adjacent to Mongolia and China.

COVID-19 and entrepreneurship entry and exit: Opportunity amidst adversity.

We theoretically and empirically examine how acquiring new skills and increased financial worries influenced entrepreneurship entry and exit intentions during the pandemic. To that end, we analyze primary individual-level survey data we collected in the aftermath of the COVID-19's first wave in Russia, which has had one of the highest COVID-19 infection rates globally. Our results show that acquiring new skills during the pandemic helped owners keep their existing businesses and encouraged start-ups in sectors other than information technology (IT). For IT start-ups, having previous experience matters more than new skills. While the pandemic-driven financial worries are associated with business closure intentions, they also inspire new business start-ups, highlighting the pandemic's creative destruction power. Furthermore, preferences for formal employment and remote work also matter for entrepreneurial intentions. Our findings enhance the understanding of entrepreneurship formation and closure in a time of adversity and suggest that implementing entrepreneurship training and upskilling policies during recurring waves of the COVID-19 pandemic can be an important policy tool for innovative small business development.

GSK3-mediated phosphorylation of DEK3 regulates chromatin accessibility and stress tolerance in Arabidopsis.

Chromatin dynamics enable the precise control of transcriptional programmes. The balance between restricting and opening of regulatory sequences on the DNA needs to be adjusted to prevailing conditions and is fine-tuned by chromatin remodelling proteins. DEK is an evolutionarily conserved chromatin architectural protein regulating important chromatin-related processes. However, the molecular link between DEK-induced chromatin reconfigurations and upstream signalling events remains unknown. Here, we show that ASKß/AtSK31 is a salt stress-activated glycogen synthase kinase 3 (GSK3) from Arabidopsis thaliana that phosphorylates DEK3. This specific phosphorylation alters nuclear DEK3 protein complex composition and affects nucleosome occupancy and chromatin accessibility that is translated into changes in gene expression, contributing to salt stress tolerance. These findings reveal that DEK3 phosphorylation is critical for chromatin function and cellular stress response and provide a mechanistic example of how GSK3-based signalling is directly linked to chromatin, facilitating a transcriptional response.

Modern Approaches to Acellular Therapy in Bone and Dental Regeneration.

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.

Waxing power, waning pollution: The effect of COVID-19 on Russian environmental policymaking.

Like most countries globally, COVID-19 continues to have a demonstrable health, economic, and environmental impact on Russia. The purpose of this paper is to examine the possible ramifications for environmental quality in Russia during and following the coronavirus pandemic. Our work builds on the framework of Elinor Ostrom, as we argue that the pandemic and subsequent lockdown in Russia has highlighted the need for a more polycentric, de-centralized approach to environmental protection. We provide evidence for this point using a novel econometric strategy: given the tight centralization of environmental policymaking, we proxy for de facto decentralization using the amount of influence a regional governor has at the federal level. Using timely data on pollution in major Russian cities both before and during the pandemic, we employ an instrumental variable analysis which shows that pollution in a particular Russian region is negatively related to the amount of influence a Russian governor has at the federal level. Thus, the more powerful a governor is in their ability to set their own course, the better results they have in environmental quality. We conclude that Russia's environmental policy needs a fundamental rethink - and extensive decentralization - in a post-COVID-19 world.

An open, non-randomised, phase 1/2 trial on the safety, tolerability, and immunogenicity of single-dose vaccine "Sputnik Light" for prevention of coronavirus infection in healthy adults.

BACKGROUND: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by an evident shortage in the supply of licensed vaccines. In an effort to satisfy vaccine demands we developed a new single-dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein - "Sputnik Light". METHODS: We conducted an open label, prospective, non-randomised phase 1/2 trial aimed to assess safety, tolerability, and immunogenicity of "Sputnik Light" vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-CoV-2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). FINDINGS: Most of the solicited adverse reactions were mild (66·4% from all vaccinees), few were moderate (5·5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-CoV-2 antibodies revealed a group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data based on pre-existing immunity to SARS-CoV-2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594·4 at a baseline up to 26899 comparing to 29·09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time, in the seropositive group, seroconversion rate by day 42 was 92·9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81·7% (76/93) and 92·9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15·18 and 579·7 in the seronegative and seropositive groups, respectively. Antigen-specific T cell proliferation, formation of IFNy-producing cells, and IFNy secretion were observed in 96·7% (26/27), 96% (24/25), and 96% (24/25) of the seronegative group respectively and in 100% (3/3), 100% (5/5), and 100% (5/5) of the seropositive vaccinees, respectively. INTERPRETATION: The single-dose rAd26 vector-based COVID-19 vaccine "Sputnik Light" has a good safety profile and induces a strong humoral and cellular immune responses both in seronegative and seropositive participants. FUNDING: Russian Direct Investment Fund.