Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s). VHH fusion with the canonical immunoglobulin Fc fragment allows the Fc-fusion single-domain antibodies (VHH-Fc) to significantly increase their neutralizing activity and serum half-life. Previously we have developed and characterized VHH-Fc specific to botulinum neurotoxin A (BoNT/A), that showed a 1000-fold higher protective activity than monomeric form when challenged with five times the lethal dose (5 LD50) of BoNT/A. During the COVID-19 pandemic, mRNA vaccines based on lipid nanoparticles (LNP) as a delivery system have become an important translational technology that has significantly accelerated the clinical introduction of mRNA platforms. We have developed an mRNA platform that provides long-term expression after both intramuscular and intravenous application. The platform has been extensively characterized using firefly luciferase (Fluc) as a reporter. An intramuscular administration of LNP-mRNA encoding VHH-Fc antibody made it possible to achieve its rapid expression in mice and resulted in 100% protection when challenged with up to 100 LD50 of BoNT/A. The presented approach for the delivery of sdAbs using mRNA technology greatly simplifies drug development for antibody therapy and can be used for emergency prophylaxis.

Tuberculosis is known to be the biggest global health problem, causing the most deaths by a single infectious agent. Vaccine-development efforts are extremely important. This paper represents the results of the first-in-human trial of recombinant subunit tuberculosis vaccine GamTBvac in a Phase I study. GamTBvac is a new BCG booster candidate vaccine containing dextran-binding domain modified Ag85a and ESAT6-CFP10 MTB antigens and CpG ODN adjuvant, formulated with dextrans. Safety and immunogenicity of GamTBvac were estimated in an open-label clinical trial on 60 Mycobacterium tuberculosis uninfected (MTB-uninfected) volunteers previously-vaccinated with Bacillus Calmette—Guérin vaccine (BCG). The candidate vaccine had an acceptable safety profile and was well-tolerated. Three different vaccine doses with a double-immunization scheme were assessed for immunogenicity and induced a significant increase in IFN-γ in-house IGRA response and IgG ELISA analysis. Among them, the half dose vaccine group (containing DBD-ESAT6-CFP10, 12.5 μg; DBD-Ag85a, 12.5 μg; CpG (ODN 2216), 75 μg; DEAE-Dextran 500 kDa, 250 μg; and Dextran 500 kDa, 5 mg) provided high, early and stable in time immune response specific to both protein antigen fusions and is proposed for the further studies.

An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of disease severity and mortality in patients with COVID-19. Longitudinal analysis of cytokine release can expand our understanding of the initial stages of disease development and help to identify early markers serving as predictors of disease severity. In this study, we performed a comprehensive analysis of 46 cytokines (including chemokines and growth factors) in the peripheral blood of a large cohort of COVID-19 patients (n=444). The patients were classified into five severity groups. Longitudinal analysis of all patients revealed two groups of cytokines, characterizing the “early” and “late” stages of the disease course and the switch between type 1 and type 2 immunity. We found significantly increased levels of cytokines associated with different severities of COVID-19, and levels of some cytokines were significantly higher during the first three days from symptom onset (DfSO) in patients who eventually required intensive care unit (ICU) therapy. Additionally, we identified nine cytokines, TNF-α, IL-10, MIG, IL-6, IP-10, M-CSF, G-CSF, GM-CSF, and IFN-α2, that can be used as good predictors of ICU requirement at 4-6 DfSO.

GamTBvac is a candidate tuberculosis vaccine with two fusion proteins, containing Ag85a, ESAT6, CFP10, and a dextran-binding domain (DBD). Phase II of a double-blind, randomized, multicenter, placebo-controlled study in parallel groups in healthy adults to evaluate the safety and immunogenicity of GamTBvac in 180 previously-vaccinated with Bacillus Calmette–Guérin vaccine (BCG) healthy volunteers without Mycobacterium tuberculosis (MTB) infection was conducted. The dose (0.5 mL) of either the study drug or a placebo was administered subcutaneously twice with an 8-week interval. At eight timepoints from 14 to 150 days, whole blood and sera were assayed. Antigen-specific T-cell responses were measured by an in-house interferon-gamma release assay (IGRA-test), the QuantiFERON (QTF) test, and intracellular cytokine staining (ICS). For antibody response detection, the bead-based multiplex immunoassay (MIA) was applied. The vaccine confirmed an acceptable safety profile previously shown in a first-in-human clinical study. After stimulation with both fusions, the highest median level of INF-γ was detected on day 21. The GamTBvac vaccine induced antigen-specific interferon-gamma release, Th1 cytokine-expressing CD4+ T-cells, and IgG responses and results support further clinical testing of GamTBvac.

Objectives Vaccination remains the most effective response to the COVID-19 pandemic. Most vaccines use two-dose regimens. In turn, single-dose vaccines also have high potential, since, on the one hand, they simplify the vaccination program, make it more accessible and convenient for more people around the world, and on the other hand, they are better suited for subsequent revaccination. However, there is not enough data on the effectiveness of single-dose vaccine variants against new genetic lines to assess their current potential. It is not clear how much a single dose of immunization protects against the globally dominant delta variant. In this work, we investigated the effectiveness of a single dose vaccine (Sputnik Light, the first component of Sputnik V vaccine) against the Delta variant in Moscow. Methods To assess the effectiveness of one dose of viral vector vaccine based on rAd26 against the delta variant in Moscow, we used data from the Moscow registries of vaccination against COVID-19 and the incidence of COVID-19. The availability of data on the number of seropositive residents of Moscow made it possible to consider the size of the immune layer formed because of a previous COVID-19 disease or vaccination. To calculate the effectiveness, the proportion of COVID-19 cases among those vaccinated with a single dose and the proportion of cases among those who were not vaccinated in July 2021. Results Our data indicate that throughout July 2021, the dominant variant of the coronavirus at the level of 99.5% in Moscow was the SARS-CoV-2 delta variant and its subsidiary lines. Considering the immune layer of 46% allowed us to calculate the effectiveness of a one-shot vaccine against the delta variant in Moscow during the first three months after vaccination at the level of 69.85% (95% confidence interval [CI], 64.08 to 74.70). In the 18-29-year-old group, the overall vaccine efficacy against the delta variant was 88.61%, in the 18-59 group - 75.28%. Sputnik Light demonstrates higher efficacy against Delta variant than many two-shot vaccines. Conclusion The results indicate a high efficacy of a single immunization first component of Sputnik V vaccine against delta variant among young and middle-aged people (86.2% and 75.28%, respectively), at least during the first 3 months after receiving the one-shot vaccine.

Mass vaccination campaigns against COVID-19 affected more than 90% of the population in most developed countries. The new epidemiologic wave of COVID-19 has been ongoing since the end of 2021. It is caused by a virus variant B.1.1.529, also known as “Omicron” and its descendants. The effectiveness of major vaccines against Omicron is not known. The purpose of this study is to evaluate the efficacy of the Sputnik V vaccine. The main goal is to assess its protection against hospitalization in the period of Omicron dominance. We conducted our study based on a large clinical center in Moscow (Russia) where 1112 patients were included. We used the case-population method to perform the calculations. The data we obtained indicate that the Omicron variant causes at least 90% of infections in the studied cohort. The effectiveness of protection against hospitalization with COVID-19 in our study was 85.9% (95% CI 83.0–88.0%) for those who received more than one dose. It was 87.6% (95% CI 85.4–89.5%) and 97.0% (95% CI 95.9–97.8%) for those who received more than two or three doses. The effectiveness in cases of more severe forms was higher than for less severe ones. Thus, present study indicates the high protective efficacy of vaccination against hospitalization with COVID-19 in case of Omicron lineage.

The avidity index (AI) of IgG to the RBD of SARS-CoV-2 was determined for 71 patients with a mild (outpatient) course of COVID-19, including 39 primarily and 36 secondarily reinfected, and 92 patients with a severe (hospital) course of COVID-19, including 82 primarily and 10 secondarily infected. The AI was shown to correlate with the severity of repeated disease. In the group of outpatients with a mild course, the reinfected patients had significantly higher median AIs than those with primary infections (82.3% vs. 37.1%, p < 0.0001). At the same time, in patients with a severe course of COVID-19, reinfected patients still had low-avidity antibodies (median AI of 28.4% vs. 25% in the primarily infected, difference not significant, p > 0.05). This suggests that the presence of low-avidity IgG to RBD during reinfection is a negative prognostic factor, in which a patient’s risk of developing COVID-19 in a severe form is significantly increased. Thus, patients with IgG of low avidity (AI ≤ 40%) had an 89 ± 20.5% chance of a severe course of recurrent COVID-19, whereas the detection of high-avidity antibodies (AI ≥ 50%) gave a probability of 94 ± 7.9% for a mild course of recurrent disease (p < 0.05).

Vaccination against COVID-19 has occurred in Russia for more than two years. According to the Russian official clinical guidelines to maintain tense immunity in the conditions of the ongoing COVID-19 pandemic, it is necessary to use booster immunization six months after primary vaccination or a previous COVID-19 contraction. It is especially important to ensure the maintenance of protective immunity in the elderly, who are at risk of severe courses of COVID-19. Meanwhile, the immunological effectiveness of the booster doses has not been sufficiently substantiated. To investigate the immunogenicity of Sputnik V within the recommended revaccination regimen and evaluate the effectiveness of booster doses, we conducted this study on 3983 samples obtained from individuals previously vaccinated with Sputnik V in Moscow. We analyzed the level of antibodies in BAU/mL three times: (i) six months after primary immunization immediately before the booster (RV), (ii) 3 weeks after the introduction of the first component of the booster (RV1), and (iii) 3 weeks after the introduction of the second component of the booster (RV2). Six months after the primary vaccination with Sputnik V, 95.5% of patients maintained a positive level of IgG antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. The degree of increase in the specific virus-neutralizing antibodies level after revaccination increased with a decrease in their initial level just before the booster dose application. In the group of people with the level of antibodies up to 100 BAU/mL six months after the vaccination, a more than eightfold increase (p < 0.001, Wilcoxon criterion with Bonferroni adjustment) in the level of specific antibodies was observed (Me = 8.84 (IQR: 3.63–30.61)). A significant increase in the IgG level after receiving both the first and the second booster doses occurred at the initial titer level up to 300 BAU/ mL (p < 0.001) in those who did not contract COVID-19 in the past and up to 100 BAU/mL (p < 0.001) in those who were previously infected with SARS-CoV-2. A significant increase in the antibody level after the first dose of the booster was noted for people who had up to 500 BAU/mL (p < 0.05), regardless of the previous COVID-19 infection. Thus, revaccination is most effective in individuals with an antibody level below 500 BAU/mL, regardless of the vaccinee age and COVID-19 contraction. For the first time, it has been shown that a single booster dose of the Sputnik vaccine is sufficient to form a protective immunity in most vaccinees regardless of age and preexisting antibody level.