Gamalei Institute of Epidemiology and Microbiology

A cross-immunity model for influenza A(H3N2) based on convolutional neural networks (CNNs) was developed and validated under temporally structured conditions that mimic real-world forecasting. Antigenic distance was derived from hemagglutination inhibition (HI) titers. The model was trained on WHO data (2011-2023) and tested in a time-split fashion on independent recent data (2022-2024). Hemagglutinin sequences (HA/HA1) were encoded into 3D tensors using five physicochemical indices from AAindex. Two- and three-layer CNN architectures were tested. Performance was evaluated using Accuracy, Sensitivity, Specificity, and Matthews Correlation Coefficient (MCC) with 95% confidence intervals. Validation on the classic Smith's dataset showed high accuracy (Accuracy = 0.9996, MCC = 0.9964), serving as a necessary sanity check. Testing on current data yielded lower but robust results (Accuracy: 0.73-0.81, MCC: 0.48-0.60), reflecting real-world forecasting complexity. ROC analysis confirmed the strong discriminative ability (AUC ≥ 0.805) and good calibration (Brier scores ≤ 0.192). The three-layer CNN demonstrated greater robustness on challenging data. This CNN model is an effective tool for assessing influenza A(H3N2) antigenic distances and holds promise for integration into epidemiological models to aid vaccine strain selection. Further accuracy improvements may arise from modeling the structural impact of amino acid substitutions and polyclonal immune responses.

Introduction. HIV infection remains a global public health problem. One of the key elements in the system of measures aimed at controlling HIV-infection is molecular genetic surveillance. The data obtained make it possible to solve a number of problems in the field of practical epidemiology, and are also of fundamental importance, expanding the understanding of the mechanisms underlying the variability of HIV-1. Most often, the HIV-1 genetic variant is determined by analysing the pol gene region. However, a number of studies are currently underway to investigate other fragments of the HIV-1 genome, such as genes coding its non-structural proteins. The aim of the study is to assess the role of regions of the genome encoding non-structural proteins of HIV-1 in determining its genetic variant, in particular, for viruses circulating in Russia. Materials and methods. Genomic maps of reference sequences of HIV-1 circulating recombinant forms and the HIV-1 nucleotide sequences obtained from HIV-infected patients were analyzed. The study design included stages collection of biosamples, proviral DNA extraction, amplification, sequencing, identification of HIV-1 genetic variants and analysis of the obtained data. Recombination breakpoints frequencies in different regions of the genome were compared using the Mann–Whitney criterion with Bonferroni multiplicity correction and chi-square with Benjamin–Hochberg multiplicity correction. Results. It was found that among the regions of the HIV-1 genome encoding its structural proteins, the most frequent recombination breakpoints occurred in pol (RT) (p 0.001/0.002); among the regions encoding non-structural proteins — in nef (p 0.001/0.007/0.018). At the same time, the genotyping of the nef gene region more often (in 38% of cases) influenced the final HIV-1 genetic variant determination when assessed on a random sample of patients. Conclusion. The regions of the HIV-1 genome with a high frequency of recombination breakpoints were determined.

This review provides a comprehensive analysis on the immunopathogenesis of neurosyphilis and discusses the related clinical perspectives. Neurosyphilis remains one of the most complex and variable forms of syphilitic infection, driven by the interaction between T. pallidum and host innate and adaptive immune cells leading to chronic inflammation and damage to the nervous system. The article highlights three major relevant areas. 1) Cellular and molecular mechanisms. The role of different T-lymphocyte subsets, cytokine cascades, macrophages, and microglia in shaping persistent inflammation, disrupting immune control, and contributing to neurodegenerative processes is examined. In particular, it emphasizes the imbalance between pro- and anti-inflammatory cytokines, as well as the strategies by which the pathogen evades immune surveillance. 2) Clinical manifestations and diagnostic approaches. Current knowledge of the wide clinical spectrum of neurosyphilis is summarized, ranging from asymptomatic forms to severe progressive neurological involvement. Special attention is given to biomarkers, including cerebrospinal fluid indices and immunological tests, as well as instrumental methods such as MRI, serological, and molecular assays, which help refine disease staging and assess activity. 3) Therapeutic opportunities and prospective targets. Existing antibiotic regimens are discussed, along with the challenges of limited efficacy and potential antibiotic resistance. The review further explores the potential of immunotherapy and combined strategies aimed at restoring immune control and reducing central nervous system inflammation. Overall, the review integrates fundamental aspects of immunopathogenesis with practical clinical considerations. By linking cellular and molecular insights with diagnostic and therapeutic perspectives, it provides a relevant resource for both clinicians and researchers primarily engaged in the search for innovative therapeutic strategies against neurosyphilis.

Vif and Vpr are HIV-1 accessory proteins that create optimal conditions for viral replication. They are considered as potential targets for the development of therapeutic agents. Natural amino acid substitutions in these proteins have previously been associated with disease progression. The aim of this study was to analyze the genetic diversity of Vif and Vpr in HIV-1 group M clades. A total of 5286 sequences were downloaded and analyzed. For 37 clades in group M, the consensus sequences, amino acid natural variation, and clade-specific amino acid residue substitutions (CSSs) were evaluated. Structural analysis and modeling of consensus sequences were performed for subtypes A1, B, C, and D. The average conservation degree in the HIV-1 group M was 86.4% for Vif and 91.3% for Vpr. In both proteins, the lowest amino acid diversity was observed in sub-subtype A6, and the highest in subtype B. In consensus sequences, the substitutions, which might influence pathogenesis, have been determined: in Vif—22H (11_cpx, 91_cpx) and 136P (A6, 01_AE, 15_01B, 59_01B, 89_BF1, 103_01B, 111_01C, 133_A6B), in Vpr—41N (06_cpx) and 55A (B, 07_BC, 35_01D, 56_cpx, 66_cpx, 66_BF1, 71_BF1, 85_BC, 137_0107). In functional motifs, CSSs associated with changes in the chemical properties of amino acid residues were noted. These findings could be taken into account for the development of therapeutic drugs in the future. No correlation was observed between the subtypes and the spatial organization of the oligomeric structures of Vif and Vpr. Using the structural analysis and modeling, it has been shown for the first time that Vif can interact with APOBEC3G as an oligomer.

The studies conducted and published in this issue highlight the potential of new peptides as a basis for developing new antibacterial drugs, especially in the face of growing antibiotic resistance [...].

The object of our study is a barrier discharge in a capillary quartz tube blown with argon flow at atmospheric pressure. The discharge was powered by sinusoidal voltage with a frequency of 125 kHz. We present the experimental results on time-spatial behavior of the plasma structures arising both inside a discharge tube and in the plasma jet. Using high-speed and multi-frame Intensified Charge Coupled Device (ICCD) imaging of the discharge, it was revealed that the formation of the diffuse and constricted plasma structures inside the discharge zone and in plasma jet. The constricted plasma structures have a “memory,” that is, they save their spatial shape in time but not more than 100–150 μs. This time interval is much shorter compared to the time spent by gas flow to pass the discharge zone inside the tube. The plasma structures were formed jointly by the diffuse and constricted surface ionization waves arising and disappearing each half-cycle of the applied voltage. The revealed diffuse surface ionization waves are identical to well-known ionization waves (in fact, surface ionization waves) propagating inside a long capillary tube, but constricted surface ionization waves are similar to those propagating along a flat dielectric barrier in a pin-to-plane surface barrier discharge. Additionally, it was shown mathematically that the linear diffusion equation for plasma potential can be applied to describe the propagation of the diffuse surface ionization wave.

Lassa hemorrhagic fever is an acute human infectious disease with high mortality rate and pandemic potential. To date, there are no approved drugs for the specific treatment or prevention of Lassa hemorrhagic fever in the world. The aim of this study was to develop and evaluate the immunobiological properties and preclinical safety of a candidate vaccine for the prevention of Lassa hemorrhagic fever (LHF) based on recombinant human adenoviral vectors. Standard genetic engineering techniques, molecular biology techniques, virological methods, and animal testing procedures were used in the course of the study. A combined vector candidate vaccine for the prevention of Lassa hemorrhagic fever has been designed and characterized. The vaccine is composed of two components for heterologous immunization in a prime-boost regimen. Both components are based on recombinant replication-defective adenovirus vectors. The first component of the vaccine is a recombinant human adenovirus type 26; the second component is a recombinant human adenovirus type 5. Both recombinant vectors contain the codon-optimized sequence of Lassa virus glycoprotein. Two experimental batches of the candidate vaccine were produced under GMP-conditions and analyzed. The results of studies in compliance with appropriate specifications for viral vector vaccines are provided. In preclinical studies in mice, antigen-specific IgG response was detected after immunization with two vaccine components, either separately, or in a prime-boost regimen. The time dynamics of the IgG response was also studied on 42, 77, 119 and 147 days after immunization. At the same time, despite achieving 100% seroconversion, no virus neutralizing antibodies were detected in any of the samples collected from immunized mice. A biodistribution study showed that 24 hours following intramuscular injection of the vaccine components, the DNA of adenovirus vectors was detected only at the site of injection and in regional lymph nodes. Based on preclinical safety assessments (including acute toxicity, chronic toxicity, immunotoxicity, allergenic properties, reproductive toxicity), no contraindications were found for initiation of the candidate Lassa vaccine clinical trials. Taken together, the results demonstrate that the candidate vaccine for prevention of Lassa hemorrhagic fever based on recombinant adenovirus vectors types 26 and 5 is a promising drug for specific immunoprophylaxis.

Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of the ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). For VLP production, rVVs expressing Env, Gag-Pol (HIV-1/SIV), and the cowpox virus hr gene, which overcomes the restriction of vaccinia virus replication in CHO cells, were used. The CHO Lec1 engineered cell line lacking GlcNAc-TI was used for generating VLPs with Env proteins containing a cytoplasmic (CT) domain affecting the surface subunit (SU) conformation. This has created the opportunity to modulate the glycan composition, and refine the conditions for their production, and optimize approaches to overcoming HIV-1 resistance associated with abundant glycosylation.