Rotavirus infection: current state and prospects for control using RNA technologies

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Introduction

Rotavirus infection is one of the leading causes of severe diarrhea and gastroenteritis in young children. The inclusion of vaccination in national immunization schedules has significantly reduced the incidence and mortality associated with rotavirus infection. However, in low- and middle-income countries, the efficacy of Rotarix and RotaTeq remains low [1, 2]. This is due to a variety of factors, including the circulation of new genotypes, maternal antibody interference, and the characteristics of the immune response in children in regions with high infection prevalence [3]. The pathogen’s high contagiousness, its environmental stability, and its capacity for genetic reassortment pose serious obstacles to the complete control of rotavirus infection, necessitating the development of new approaches to rotavirus therapy and prevention [4].

Significant progress has been made in recent decades in understanding the molecular biology of rotavirus; however, this has not yet led to the development of effective etiotropic drugs [5]. One of the most promising approaches is the application of RNA interference—an evolutionarily conserved mechanism of post-transcriptional suppression of gene expression that allows for the targeted reduction of viral replication [6]. This approach has been actively investigated as a therapeutic strategy for infectious diseases since the 2000s; in particular, there are a number of studies demonstrating the potential use of small interfering RNAs (siRNAs) targeting conserved regions of the rotavirus genome [7].

The aim of this review is to systematize current data on the molecular biology, epidemiology, and diagnosis of rotavirus infection, as well as to conduct a comparative analysis of existing live oral vaccines and promising RNA technologies (mRNA vaccines, RNA interference) for the prevention and treatment of rotavirus infection.

Methods for Selecting and Analyzing Literature

The literature search was conducted in the following databases: PubMed, Scopus, Web of Science, ScienceDirect, Google Scholar, as well as in the Russian scientific electronic libraries eLibrary.RU and CyberLeninka for the years 2015–2026. However, in key sections (molecular biology, virus classification), earlier fundamental studies were also included. The following keywords were used to formulate the search query: rotavirus, rotavirus vaccine, mRNA vaccine, RNA interference, siRNA, miRNA, lncRNA, diagnosis, epidemiology, as well as their Russian-language equivalents. The review includes original studies, preclinical trials, and systematic reviews in English and Russian. After removing duplicates and screening, 97 sources were selected.

General Information on Rotavirus

Virus Structure and Classification

Rotavirus is a non-enveloped, double-stranded RNA virus with an icosahedral shape, belonging to the Sedoreoviridae family [8]. It consists of a three-layered capsid structure with a diameter of approximately 100 nm. The intermediate capsid has icosahedral symmetry T = 13, while the inner capsid has icosahedral symmetry T = 2* (Fig. 1).

 

Fig. 1. Schematic representation of the rotavirus capsid (a) and electrophoregram of the 11 rotavirus RNA segments (b) [5, 9]

 

Rotavirus contains a genome consisting of 11 segments. These segments encode 6 structural proteins (VP1–VP4, VP6, and VP7) and 6 non-structural proteins (NSP1–NSP6). Each genome segment (with the exception of gene 11, which encodes NSP5 and NSP6) encodes a single viral protein. The outer protein layer consists of the VP4 protein (P-protein, protease-sensitive protein) and VP7 (G-protein, glycoprotein), the two major viral antigens. These proteins are targets for neutralizing antibodies and are currently of greatest interest in terms of vaccine development. The inner protein layer consists of VP6 protein trimers (I-protein). The VP6 protein is the target of most antibodies studied in enzyme-linked immunosorbent assay (ELISA) [10].

The G and P proteins of Rotavirus A are classified based on their antigenic and molecular properties: at least 42 G-protein types and 58 P-protein types have been identified, of which G1, G2, G3, G4, G9, G12, P4, P6, and P8 are the most common in human infections [11]. The distribution of genotypes varies from region to region and, to some extent, over time [12].

According to the International Committee on Taxonomy of Viruses, rotaviruses are classified into 9 species (RVA–RVJ), differentiated based on the antigenic properties of the VP6 protein of the inner capsid [13]. Among this taxonomic diversity, rotavirus A (RVA, Rotavirus alphagastroenteritidis species) is of dominant epidemiological importance and is considered the most widespread and clinically significant pathogen for humans. It has been established that RVA accounts for more than 90% of all cases of acute viral gastroenteritis in the global population [14].

Viral Replication

The rotavirus replication cycle occurs in the cytoplasm of the host cell and includes stages such as adsorption, entry into the host cell, transcription/translation of viral proteins, genome replication, virion assembly, and release of mature particles (Fig. 2).

 

Fig. 2. The rotavirus replication cycle [9].

 

The virus binds to receptors on the surface of intestinal enterocytes—integrins α2β1 and αvβ3, and the heat shock protein hsp70—via the outer capsid proteins VP4 and VP7 [15, 16]. Adsorption is mediated by the VP4 protein or its proteolytic cleavage product, VP8* [15]. Internalization occurs via clathrin-mediated endocytosis. It takes 40–60 minutes from receptor binding to entry into the cytoplasm [17]. In the endosome, under the influence of a reduced concentration of Ca²⁺ ions, the VP7 trimer dissociates, which initiates conformational changes in the VP4 protein. The transcriptionally active double-stranded particle (DSP) is released into the cytoplasm [17, 18]. Inside the double-stranded particle, RNA-dependent RNA polymerase (VP1) synthesizes the sense-strand RNA from each segment of the genomic double-stranded RNA (dsRNA). The RNA plus-strands are capped by guanylyl transferase (VP3) and enter the cytoplasm through pores, where they serve as a template for the translation of viral proteins [19]. Translation of viral mRNAs that lack a poly-A sequence at the 3'-end is facilitated by the NSP3 protein, which displaces the poly-A-binding protein from the complex with the translation initiation factor eIF4G, leading to the termination of cellular mRNA translation [20, 21].

Within the virions, the positive-strand RNA is packaged with the VP1, VP2, and VP3 proteins, and the complementary negative-strand RNA is synthesized to form dsRNA [22, 23]. After synthesis, dsRNA remains bound to subviral particles; free dsRNA is not detected in cells, and the NSP2 and NSP5 proteins participate in genome packaging [24].

A distinctive feature of rotavirus morphogenesis is that subviral particles, which are assembled in the viroplasm, exit through the endoplasmic reticulum membrane, temporarily acquiring a lipid envelope [25]. The NSP4 protein plays a key role in this process: as a viroporin, it increases cytoplasmic Ca²⁺ levels, which are necessary for replication and morphogenesis, and also ensures the correct folding of the VP7 protein and the formation of its structural epitopes [26]. Within the endoplasmic reticulum lumen, the temporary membrane envelope is shed and replaced by the outer capsid proteins VP7 and VP4, resulting in the formation of mature three-layered viral particles, which are released from the cell upon its lysis [27]. The infection cycle is completed on average 6–15 hours after entry into the cell, and cell lysis is accompanied by the release of viral proteins, including the NSP4 protein, which plays a key role in the pathogenesis of rotavirus infections [25].

Clinical manifestations of rotavirus infection

The clinical presentation of rotavirus infection ranges from mild diarrhea to severe forms with significant dehydration [28, 29]. The most characteristic symptoms of the disease are fever, vomiting, and diarrhea; a distinctive feature of rotavirus gastroenteritis is that these symptoms are more severe compared to infections caused by other intestinal viruses [5, 28]. Physical examination reveals abdominal cramps, signs of dehydration (dry mucous membranes, decreased skin turgor, tachycardia, oliguria), as well as marked weakness and fatigue [30]. Rotavirus infection progresses in three phases: the incubation period (1 to 4 days), the acute phase (3 to 7 days or longer in severe cases), and the convalescent phase (4–5 days); in immunocompromised children, chronic infection may develop [31].

Epidemiology

Transmission of the pathogen occurs primarily via the fecal-oral route. Rotavirus is highly stable in the external environment and can remain infectious for several months. The virus is shed in high concentrations in feces and vomit throughout the course of the illness [29]. It is important to note that asymptomatic forms of rotavirus infection are also accompanied by viral shedding and serve as a source of transmission [32].

Annually, between 122,000 and 215,000 deaths among children under 5 years of age from rotavirus infection are recorded worldwide, with more than 90% of these occurring in low- and middle-income countries [33]. The highest mortality rates are recorded in South Asian countries and sub-Saharan Africa [34].

The 10 countries with the highest mortality rates from rotavirus infection include India, Pakistan, Nigeria, the Democratic Republic of the Congo, Ethiopia, Kenya, Niger, Angola, Afghanistan, and Chad [35]. Countries with a temperate climate are characterized by a distinct autumn-winter seasonality of rotavirus infection [36], which is traditionally associated with a seasonal decrease in temperature and humidity. In tropical regions, rotavirus infection is reported year-round, without pronounced peaks.

In regions with an unfavorable epidemic situation, primary infection occurs at an earlier age: the peak incidence occurs at 5 months of age compared to 20 months in developed countries, which is associated with increased mortality [37]. In addition to the age factor, the increased mortality in these regions is due to malnutrition, limited access to preventive and therapeutic measures, as well as a high prevalence of comorbidities [38].

In Russia, according to Rospotrebnadzor, rotavirus infection will remain the leading cause of acute intestinal infections, accounting for 36.82% of the total number of cases. The rotavirus infection incidence rate in 2024 (63.14 per 100,000 population) is 5.9% higher than the 2023 rate, but does not exceed the long-term average (73.95 per 100,000 population). The highest rotavirus incidence rates were recorded among children aged 1 to 2 years—1,058.76 per 100,000 people—and among children under 1 year of age—721.30 per 100,000. There is a significant variation in incidence rates across regions. The highest level of rotavirus infection among children under 1 year of age was recorded in the Republic of Tuva (41%), the Republic of North Ossetia–Alania (41%), Kaluga region (33%), the Republic of Dagestan (32%), and the Kabardino-Balkar Republic (32%), where the proportion of children under 1 year of age among those who fell ill exceeds the national average [39].

Despite the annual increase in the number of vaccinated infants since the inclusion of the rotavirus vaccine in the national immunization schedule based on epidemiological indications, coverage of the target cohort nationwide remains critically low: in 2022 it was only 7.15%, and in 2023—12.07%, which is insufficient to influence the epidemic process. High vaccination rates (over 50–80%) have been achieved only in certain regions (Sakhalin region, Yamalo-Nenets Autonomous district, the Republic of Buryatia, and Khanty-Mansi Autonomous district).

Diagnosis of Rotavirus infection

The clinical presentation of rotavirus infection is characterized by the absence of specific symptoms, which makes it difficult to distinguish it from acute intestinal infections of other etiologies based solely on medical history and physical examination findings. Gastroenteritis caused by rotaviruses, noroviruses, astroviruses, adenoviruses, enteroviruses, as well as bacterial pathogens (Escherichia coli, Salmonella spp., and others), exhibits significant clinical similarities, necessitating laboratory diagnosis, which is the only reliable method for confirming the etiology of rotavirus infection. However, in clinical practice, it is not always performed due to the lack of etiological treatment for viral diarrhea, and in most cases, the diagnosis is established based on the clinical picture as “A08.4—Viral intestinal infection, unspecified.” Laboratory verification of the virus is performed in cases of severe, protracted, or atypical disease progression, as well as within the framework of epidemiological surveillance, after which the diagnosis may be specified as “A08.0 — Rotavirus enteritis” [39].

Overall, identifying the pathogen of acute intestinal infections can be economically justified, as these results contribute to more thorough epidemiological surveillance and are also important for post-marketing studies on the efficacy of vaccines against the pathogens of acute intestinal infections. The most widely used test in clinical practice is the colloidal gold immunochromatographic assay, which is designed to detect viral antigens in stool samples, is simple to perform, and is considered a rapid test [40]. ELISA for the detection of rotavirus antigen has shown a high rate of false-positive and false-negative results in clinical practice, which necessitated a modification of this method—the use of biotin-avidin sandwich systems employing monoclonal antibodies against the VP6 antigen [40, 41].

Nucleic acid amplification methods offer significantly higher sensitivity and specificity. Polymerase chain reaction (PCR) and its modification—real-time quantitative PCR with reverse transcription—allow not only for the detection of viral RNA in the early stages of rotavirus infection but also for the genotyping of isolates [5, 42, 43]. Currently, real-time PCR with reverse transcription is considered the reference method (gold standard) for laboratory diagnosis of rotavirus [44]. Digital PCR is also a promising area of development in molecular diagnostics. This method is based on dividing the sample into thousands of individual reaction mixtures in microplates, which allows for the determination of the absolute amount of viral RNA without the use of standard curves. Digital PCR is characterized by high sensitivity, which is necessary for detecting low concentrations of the virus in biological samples, and also allows for the detection of rare genetic variants (single-nucleotide polymorphisms) in the rotavirus genome. Although this method has not yet found widespread use in routine clinical practice, it is actively used in epidemiological surveillance (including wastewater analysis to assess the prevalence of infection in the population) and in scientific research aimed at studying the genetic diversity and evolution of the virus [41, 45].

Despite their high effectiveness, traditional methods (PCR) have a number of limitations, including labor intensity, the necessity for expensive equipment, and the requirement for highly qualified personnel. Consequently, isothermal amplification methods have seen active development and can serve as an alternative for rapid diagnostics. Among these, loop-mediated isothermal amplification (LAMP) and recombinase-mediated polymerase amplification have become the most widely used. LAMP is characterized by high sensitivity and specificity, as well as being less labor-intensive compared to conventional PCR. However, LAMP places increased demands on the design of specific primers (requiring the use of multiple pairs) and carries a risk of false-positive results [44, 46]. Compared to LAMP, recombinase-mediated polymerase amplification technology is simpler and faster to perform, while allowing for an extremely low pathogen detection threshold [47].

Current Approaches to the Treatment and Prevention of Rotavirus Infection

Currently, there are no approved antiviral drugs for the elimination of rotavirus. Consequently, treatment for rotavirus infection is aimed at relieving clinical symptoms and preventing associated dehydration. The most effective method in pathogenetic therapy for mild and moderate dehydration is oral rehydration. It is aimed at correcting the water-electrolyte balance through the use of oral rehydration salts, which contain an optimal ratio of glucose and sodium [41, 48]. Intravenous infusions are indicated in cases of severe dehydration or when oral fluid intake is not possible.

A number of studies demonstrate the efficacy of certain probiotic strains, such as Lactobacillus rhamnosus GG, Bifidobacterium longum, B. lactis, L. reuteri, L. acidophilus LB, Saccharomyces boulardii, and others. The application of probiotics in children with rotavirus diarrhea helps reduce the duration of the diarrheal syndrome and hospitalization, and improves immunological parameters [41, 49, 50]. Enterosorbents—dioctahedral smectite and other drugs—are widely used in clinical practice. They adsorb viral particles, toxins, and gases onto their surface, reducing the duration and severity of diarrhea. Sorbents promote stool formation and reduce the load on enterocytes.

Studies published between 2014 and 2025 confirm the therapeutic potential of immunoglobulins in the treatment of rotavirus infections in children [41]. Randomized controlled trials and observational studies have shown that the use of immunoglobulins, particularly oral IgY antibodies, helps reduce the duration of diarrhea, shorten the duration of viral shedding, and strengthen the local immunity of the intestinal mucosa.

Vaccination is the most effective means of controlling the incidence of rotavirus infection. Currently, the following oral vaccines are approved for use in clinical practice: Rotarix, containing a single strain of human rotavirus (G1P[8]) (GlaxoSmithKline); RotaTeq, containing 5 rotavirus strains (G1, G2, G3, G4, and P[8]) derived from both human and animal rotaviruses (Merck and Co.); Rotavac, containing a local human rotavirus strain (G9P[11]) (Bharat Biotech International Ltd.); Lanzhou Lamb Rotavirus (LLR) vaccine, derived from a rotavirus strain isolated from lambs, specifically targeting genotype G10P[15] (Lanzhou Institute of Biological Products); Rotavin-M1, derived from a human rotavirus strain specifically targeting genotype G1P[8] (POLYVAC-Vietnam); and RotaSiil, containing 5 reassortant human rotaviruses (G1, G2, G3, G4, G9; Serum Institute of India Ltd.) [51]; ROTA-V-EID, which is the same pentavalent reassortant vaccine (G1, G2, G3, G4, G9) as RotaSiil (Serum Institute of India Ltd.). ROTA-V-EID is approved by the WHO for the prevention of rotavirus infection and is the only rotavirus vaccine currently available in Russia.

In addition to inactivated and live vaccines, it is worth noting that recombinant and subunit vaccines against rotavirus infections are also currently under development and active research. The most widely reported in the literature is a parenterally administered vaccine based on the truncated VP4(MZ8*) protein, available in monovalent and trivalent forms. Safety and immunogenicity studies of this monovalent formulation in the United States and South Africa showed that the vaccine is safe and well-tolerated; a trivalent formulation was later developed to improve heterotypic immune coverage [52]. This P2-VP8 subunit-based vaccine demonstrated good results in Phase II clinical trials: adequate tolerability and immunogenicity with a sustained response of neutralizing antibodies and serum IgG across all three P-type vaccine strains [53].

Phase III clinical trials of the trivalent rotavirus P2-VP8 subunit vaccine have been completed (ClinicalTrials.gov: NCT04010448); however, no published results are available that would allow for a more precise assessment of its immunogenicity and efficacy.

Bovine-human recombinant (BRV) vaccines are also currently under active development, including a quadrivalent UK-BRV (Shanta Biotechnics), a pentavalent UK-BRV (Instituto Butantan), and a hexavalent UK-BRV (Wuhan Institute of Biological Products) [54]. The quadrivalent UK-BRV has been shown to be similar in effectiveness to RotaTeq [55], but development of this vaccine appears to have been discontinued.

The pentavalent UK-BRV vaccine demonstrated safety and immunogenicity in a Phase I study, but no further clinical trials of this vaccine candidate were conducted [56, 57].

Results from Phase I clinical trials of the hexavalent UK-BRV vaccine were also recently published, indicating that this candidate is safe for adults, infants, and young children, and is immunogenic in infants, as evidenced by higher IgA seroconversion rates in the vaccinated groups compared to the placebo group [58]. It is believed that Phase III trials of this UK-BRV hexavalent vaccine candidate are currently underway.

It is also worth noting local developments in the field of recombinant vaccines against rotavirus infection.

I.V. Dukhovlinov and colleagues worked on the development of a vaccine based on two hybrid proteins: VP6VP8 and FliCVP6VP8. FliCVP6VP8 comprises a fragment of the VP6 protein and a fragment of the VP8 protein from rotavirus A. The VP6 protein fragment shares common and homologous regions with the VP6 protein fragment from rotavirus C. Components of Salmonella flagellin (FliC) were also incorporated into the proteins as an adjuvant. All components were linked by flexible bridges. Research results showed that recombinant proteins administered with flagellin exhibit enhanced immunogenic and antigenic properties. Responses to them are observed more rapidly and elicit a stronger cellular and humoral immune response [59].

N.S. Khudainazarova worked on the development of a new, highly immunogenic, and safe broad-spectrum candidate vaccine against rotavirus A (RVA). A recombinant RVA antigen was obtained as the basis for the candidate vaccine. This antigen includes sequences of the VP8* subunit of the rotavirus VP4 protein—the spike protein of the RVA virion capsid [60]. At present, there are no data on preclinical trials of the aforementioned vaccine candidates.

RNA technologies in the prevention of rotavirus infection — mRNA Vaccines

As a platform for vaccine development, mRNA represents a fundamentally different approach compared to traditional live-attenuated or protein subunit vaccines. Unlike classical vaccines, which contain viral proteins or attenuated virions directly, mRNA vaccines deliver genetic information encoding target viral antigens into host cells [61, 62].

The mechanism of action of mRNA vaccines is based on the use of the host cell’s machinery for the endogenous synthesis of the target antigen [51, 63]. The advantage of an mRNA vaccine for combating rotavirus infections lies in its potential to elicit a broad protective immune response through the rapid expression of specific antigens from the mRNA template. The technology for producing mRNA vaccines itself provides the most optimal and rapid approach to modifying the vaccine composition by altering the mRNA sequence to cover a greater number of circulating viral serotypes and/or in response to the rapid evolutionary variability of strains. The process of producing mRNA vaccines is more cost-effective and safer in terms of risks and restrictions for use in children and adults (since allergic reactions to cellular and embryonic components of the vaccine are eliminated). The cornerstone of mRNA vaccine development is the process of targeted intracellular delivery of mRNA. To date, there is no information on attempts to deliver mRNA vaccines to cells of the small intestine, where the infectious process occurs directly, analogous to live attenuated and recombinant vaccines [15]. The only described method of mRNA vaccine delivery is intramuscular administration of mRNA encapsulated in lipid nanoparticles (LNPs). Subsequently, the mRNA penetrates the cytoplasm of antigen-presenting cells (APCs) and myocytes [61, 64]. The viral antigen synthesized in vivo is processed and presented on the surface of antigen-presenting cells (APCs) in a complex with class I and class II major histocompatibility complex (MHC) molecules. This ensures the activation of both CD8⁺ cytotoxic T lymphocytes and CD4⁺ T helper cells, which, in turn, stimulate B cells to differentiate into antibody-secreting plasma cells [64]. Thus, mRNA vaccines mimic the natural process of viral infection with regard to antigen presentation, but without the risk of pathogen replication and disease development.

In the development of mRNA vaccines against rotavirus, the key target antigens are the structural proteins VP4 (particularly its cleaved fragment VP8*) and VP7, which contain the major neutralizing epitopes, as well as the highly conserved protein VP6.

Of particular interest is the VP4–VP8* protein fragment, which contains key neutralizing epitopes and is responsible for the virus’s binding to receptors on the surface of enterocytes [51, 64]. The selection of VP8* as a target antigen is justified by several factors. First, this protein is immunodominant: antibodies against VP8* possess pronounced virus-neutralizing activity [64]. Second, conserved regions in the VP8* structure suggest the potential for cross-protection against various rotavirus genotypes [63]. Third, the use of isolated VP8* protein in a parenteral vaccine allows for overcoming the problem of maternal antibody interference, which is characteristic of oral live vaccines [51, 63].

Another important antigen is the outer capsid glycoprotein VP7, which determines the G-serotype and plays a role in viral entry into the cell. However, VP7 is antigenically variable: antibodies to one serotype weakly neutralize viruses of other G-types, which requires the inclusion of several variants of this protein to ensure broad protection [63, 64]. Combining VP7 with VP8* and VP6 in a multivalent formulation allows for the engagement of both humoral and cellular immunity, thereby providing cross-protection [61, 65]. The rotavirus VP6 protein is highly conserved and immunogenic; unlike VP4 and VP7 proteins, it does not induce serotype-specific neutralizing antibodies but provides cross-protection. Inclusion of VP6 in an mRNA vaccine stimulates T-cell (CD4⁺/CD8⁺) and mucosal IgA-mediated immunity, which enhances long-lasting heterologous protection in combination with VP8* and VP7 [51, 65, 66].

Preclinical studies of mRNA vaccines against rotavirus and approaches to computer modeling of new candidates

The most readily available model for initial screening is the BALB/c mouse strain. S. Roier et al. administered two doses of the P2-VP8* P mRNA vaccine [8] intramuscularly to mice and compared the response with that in a group receiving the P2-VP8* P protein-adjuvant vaccine [8]. Animals vaccinated with a buffer solution served as the negative control. By day 42, the mRNA vaccine had induced neutralizing antibodies, as well as significant levels of interferon-γ⁺ and tumor necrosis factor-α⁺ in antigen-specific CD8⁺ and CD4⁺ splenocytes. In the protein vaccine group, neutralizing antibodies were virtually undetectable, and there was no T-cell response. Thus, the mRNA vaccine encoding P2-VP8* P[8] elicited a high level of both humoral and cellular immune responses in mice [64].

Concurrently, S. Lu et al. developed an mRNA vaccine encoding the VP7 protein (G1P[8]), encapsulated in LNP. Immunization of mice with 3 doses of the vaccine (2, 5, or 10 μg) administered intramuscularly or subcutaneously led to an increase in IgG antibody levels, as well as to the activation of antigen-specific CD8⁺ T cells and their production of interferon-γ. Transcriptomic analysis revealed the activation of chemokine signaling pathways and genes associated with the immune response [63].

In guinea pig models, the immune response to subunit vaccines is significantly stronger than in mouse models. This confirmed the immunogenicity of the trivalent LS-P2-VP8* mRNA vaccine, which includes genotypes P[8], P[4], and P[6] [64]. The same study found that the LS-P2-VP8* vaccine, which forms 60-mer nanoparticles through fusion with lumazinsynthase, induced both homologous neutralizing antibodies against P[8] and heterologous antibodies against P[4] and P [6].

Gnotobiotic piglets remain the most illustrative model for preclinical trials—the only model in which infection with the human Wa HRV strain (G1P[8]) leads to the development of diarrhea and the shedding of a virus similar to the human virus. In a study by S. Hensley et al., a comparative evaluation was conducted of the immunogenicity and protective efficacy of two candidate trivalent mRNA vaccines against human rotavirus, encoding the VP8* fragment of genotypes P[4], P[6], and P[8] [67]. The vaccines were designed in two variants: P2-VP8*, containing the universal T-cell epitope P2, and LS-P2-VP8*, in which P2-VP8* was fused to the lumazin synthase (LS) subunit, which enabled the formation and secretion of protein nanoparticles with VP8* presented on the surface. In the study, a three-dose intramuscular immunization regimen was administered, after which the animals were infected with the virulent Wa (G1P[8]) strain of HRV. Both mRNA vaccines, particularly LS-P2-VP8*, significantly reduced the duration and severity of diarrhea, decreased viral shedding compared to the control group of animals, induced higher titers of VP8*-specific IgG antibodies, and enhanced the cellular immune response. The results demonstrated the promising efficacy of VP8*-based mRNA vaccines in a preclinical model and provided justification for their further use as candidates for parenteral immunization against rotavirus infections.

Computer modeling methods are also used in the development of mRNA vaccines against rotavirus. In a study by S. Aram et al., based on a phylogenetic analysis of 40 VP4 protein sequences from rotavirus A, a representative sequence was selected, from which 7 cytotoxic and 10 T-helper epitopes were subsequently identified [62]. The engineered mRNA vaccine contained human beta-defensin 3 (hBD3) as an adjuvant. Molecular docking revealed stable binding to TLR2 and TLR3, and 200 ns molecular dynamics simulations confirmed the conformational stability of the TLR3–vaccine complex. The MM/GBSA method demonstrated a strong and stable interaction between the vaccine construct and the target receptor. To ensure efficient translation, codon optimization and mRNA secondary structure prediction were performed [62].

In a study by H. Wu et al., a trivalent mRNA vaccine against norovirus, rotavirus, and adenovirus 40/41 was designed, incorporating 16 cytotoxic T-cell epitopes, 5 T-helper epitopes, and 17 linear B-cell epitopes. The vaccine’s tertiary structure, predicted using AlphaFold3, was of high quality: ERRAT 90.0726, Z-score –3.53, and 96.2% of residues were located in the most favorable regions on the Ramachandran plot [65].

The efficacy of the mRNA platform has been confirmed not only in laboratory models but also in a veterinary study on pregnant mares. K.E.R. Borba et al. demonstrated that two-dose immunization of mares with a VP8*-based mRNA vaccine resulted in foals having higher levels of long-lasting circulating neutralizing antibodies against the G3 strain up to 49 days of age [68]. Although these data pertain to veterinary medicine, they further confirm the potential of mRNA technology to induce durable humoral immunity against rotavirus in large animals.

The presented studies indicate that mRNA vaccines against rotavirus are capable of inducing a durable humoral and cellular immune response in various preclinical models, and computational modeling methods provide effective tools for their rational design.

Clinical Trials of mRNA Vaccines Against Rotavirus

At present, none of the mRNA-based vaccine candidates against rotavirus infections have advanced to the clinical trial phase—all developments remain in the preclinical stage. The most promising candidate is the trivalent mRNA vaccine LS-P2-VP8 (CureVac), which encodes the VP8* fragment of the VP4 spike protein of rotavirus genotypes P[8], P[6], and P[4]. Additional preclinical studies are required to obtain approval for clinical trials [66, 67].

Unlike the mRNA candidates, the TV P2-VP8 protein vaccine has completed a full cycle of clinical trials, including Phase III (ClinicalTrials.gov: NCT04010448). Phase III results, published in 2026, showed that the trivalent vaccine did not meet its efficacy targets: the incidence of severe rotavirus gastroenteritis in the TV P2-VP8 group was 4.51% compared to 2.57% in the comparator group (ROTARIX). The relative efficacy of the vaccine was –77.68% (95% CI from –162.38 to –21.54). Interim analysis data indicated a low probability of confirming the superiority of the TV P2-VP8 vaccine over ROTARIX, and therefore the study was terminated early [69].

RNA Technologies in the Treatment of Rotavirus Infection

The search for new therapeutic strategies includes the development of drugs based on RNA interference, which is an evolutionarily conserved mechanism of post-transcriptional gene silencing mediated by small non-coding RNAs [70, 71]. The process is initiated by dsRNA, which is cleaved into short fragments 21–23 nucleotides in length—small interfering RNAs (siRNAs). After siRNA formation, they are assembled into the RNA-induced silencing complex (RISC), where strand separation occurs [71, 72]. The guide strand of the siRNA directs RISC to the complementary sequence of the target mRNA, leading to its endonuclease cleavage by the Argonaute 2 protein [70, 72].

In addition to exogenously introduced siRNAs, cells contain endogenous microRNAs (miRNAs) that are encoded by the host genome and regulate gene expression by partially binding to the 3'-untranslated region (3'-UTR) of target mRNAs, leading to the inhibition of translation or degradation of the mRNA [70, 72]. In the context of viral infections, both siRNA and miRNA can be used to suppress viral replication [71]. Rotavirus, which has a double-stranded RNA genome and a complex cytoplasmic replication cycle, is a suitable target for RNA interference, since its mRNAs become accessible to RISC in the cytosol of the infected cell [73].

Small interfering RNAs for direct suppression of viral gene expression

Despite the relative popularity of the RNA interference approach for suppressing the replication of RNA viruses during the 2000s, only a few such studies have been conducted on rotavirus. In several studies, siRNAs were used as a research tool to analyze the functions of viral proteins and their interactions with numerous cellular factors at different stages of the rotavirus life cycle, rather than as a potential therapeutic agent [76–78]. A team from the University of Mexico City (Mexico), led by C. Arias, several of whose publications were cited above, has conducted the most in-depth and consistent research in the field of rotavirus molecular biology using RNA interference.

It is also worth mentioning the study by J. Feng et al., which demonstrated a significant reduction in rotavirus replication following miRNA-mediated inhibition of the NSP4, VP7, and VP4 genes in cellular and mouse models of rotavirus infection, with anti-NSP4 miRNA exhibiting the greatest effect [79].

F. Chen et al. also successfully applied RNA interference against bovine rotavirus in both cellular and animal models of infection. To suppress the expression of the rotavirus non-structural protein NSP4 gene, two recombinant lentiviral vectors encoding short hairpin RNAs (shRNA). A significant reduction in gene expression was observed for each shRNA individually, and the combination of the two shRNAs almost completely suppressed the expression of the viral NSP4 gene. Treatment with the combination of the two shRNAs also resulted in the complete absence of diarrhea symptoms in suckling mice infected with rotavirus [80].

These studies indicate that siRNAs that suppress the NSP4 gene possess significant antiviral activity and are capable of specifically inhibiting rotavirus replication, which may have clinical applications in the future.

The efficacy of siRNA against rotavirus was also demonstrated in a study by A. Bhuinya et al., in which transfection of cells with siRNA targeting the VP4 gene led to a significant reduction in viral protein synthesis and a decrease in the yield of infectious particles [71]. A key advantage of the siRNA approach is the ability to rapidly design molecules against any viral sequences as they are sequenced, which is particularly important for combating epidemiologically relevant strains. However, the main obstacle to the clinical application of siRNA remains their delivery to target cells—small intestinal enterocytes.

Upon oral administration, naked siRNAs rapidly degrade under the effect of gastrointestinal nucleases and are unable to cross cell membranes. To address this problem, various delivery systems are being developed (liposomes, nanoparticles, conjugation with ligands) [73].

MicroRNAs as modulators of rotavirus infection

One of the most important applications of miRNA profiling has been the development of non-invasive diagnostic approaches. N. Rashid et al. demonstrated that analysis of miR-122 and miR-21 levels in children’s feces can serve as a reliable indicator of increased intestinal permeability developing against the backdrop of persistent infections, including rotavirus infections [82]. In children with increased intestinal permeability, the levels of these miRNAs are 10–11 times higher, allowing them to be used as non-invasive biomarkers of intestinal barrier dysfunction.

G. Elkady et al. applied high-throughput miRNA sequencing in MA-104 cells infected with bovine rotavirus [70]. This approach made it possible for the first time to obtain a complete picture of the transcriptomic response: 160 differentially expressed miRNAs were identified, and bioinformatics analysis of their potential targets indicated the involvement of the mTOR, NF-κB, and PI3K/Akt signaling pathways. Thus, miRNA profiling serves as a powerful tool for mapping interactions in the “virus–host” system and identifying promising molecular targets.

The role of specific miRNAs is validated using methods involving the transfection of synthetic analogs. To demonstrate the antiviral properties of miRNAs, researchers use synthetic RNA molecules—analogs of endogenous cellular miRNAs (miR-Mimics)—to increase endogenous miRNA levels, or specific inhibitors to suppress them [81]. For example, Z. Tian et al. demonstrated that transfection of miR-525-3p (whose levels decrease during rotavirus infections) led to a 70–80% reduction in viral titer, whereas the use of an inhibitor of this miRNA, conversely, enhanced its replication [72].

Similarly, H. Huang et al. demonstrated that increasing the level of miR-194-3p using a miR-Mimic of protective miRNAs suppresses the expression of the viral proteins VP6 and VP7 and also reduces the formation of infectious particles [83]. These data indicate that restoring the pool of protective miRNAs is an effective strategy for combating rotavirus infections.

Understanding the molecular mechanisms of miRNA action is impossible without identifying their target genes. The classical approach involves the use of luciferase reporter constructs. Thus, Z. Tian et al. confirmed that miR-525-3p directly binds to the 3'-untranslated region of the viral NSP1 protein, as evidenced by a decrease in luciferase activity upon co-transfection with a miR-Mimic [72]. In a study by N. Huang et al., it was shown that miR-194-3p specifically binds to the 3'-untranslated region of the cellular protein SIRT1—a key regulator of autophagy [83]. These findings not only elucidate the mechanisms of miRNA action but also identify specific links in the viral cycle and cellular metabolism that are vulnerable to therapeutic intervention.

In a number of studies, synthetic miRNA analogs have been explored as prototypes for antiviral drugs. L. Song et al. demonstrated that an inhibitor of the proviral miR-4301 is capable of reducing rotavirus replication and increasing the survival of infected cells [84]. The most promising approach was proposed by A. Banerjee et al., who used a combination of miR-Mimics of the defensive miRNAs miR-192/215 and miR-181a [85]. This approach allowed for the suppression of viral infection by simultaneously targeting several components of the Wnt/β-catenin signaling pathway. It is important to note that the virus actively evolves to suppress the host’s protective miRNAs (for example, rotavirus reduces the levels of miR-525-3p [73], miR-194-3p [73], and the miR-192 family [85]). Modulating the levels of these miRNAs using synthetic analogs allows for the restoration of disrupted defense mechanisms.

Thus, miRNAs are not only biomarkers but also active regulators of the pathogenesis of rotavirus infections. The use of their synthetic analogs (miR-Mimics of protective miRNAs and inhibitors) represents a novel approach for developing highly specific, next-generation antiviral drugs that act at the level of RNA interference.

Long non-coding RNAs as regulators of rotavirus infection

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides that can function both in the nucleus and in the cytoplasm by interacting with DNA, other RNAs, and proteins. Their primary mechanisms of action include: acting as molecular sponges for miRNAs, thereby influencing the expression of target genes; facilitating the targeted delivery of protein complexes to specific DNA sequences; and serving as a platform for the assembly of multi-protein complexes. The role of lncRNAs in rotavirus infections is in the early stages of investigation [86, 87].

The study of transcriptomic changes induced by rotavirus infections has revealed a significant number of differentially expressed lncRNAs, indicating their potential role in pathogenesis and host–virus interactions. A. Banerjee et al. used real-time PCR to identify 34 differentially expressed lncRNAs in HT-29 cells infected with rotavirus; the most significant increase was observed for lncRNA SLC7A11-AS1 (more than 10,000-fold) [86]. H. Song et al. used sequencing in MA-104 cells and identified 11,919 lncRNAs, of which 4,422 were upregulated and 233 were downregulated following rotavirus infection [87].

According to S. Banerjee et al., rotavirus induces the proviral lncRNA SLC7A11-AS1, which suppresses the expression of the xCT antiporter, depletes glutathione pools, and triggers ferroptoxis, thereby facilitating the release of viral particles from the infected cell [86]. X. Song et al. identified numerous differentially expressed lncRNAs in rotavirus infections, including lncRNA-6479 and lncRNA-4290 [80]. As previously shown, lncRNAs can regulate the expression of target genes through miRNA binding, functioning as competing endogenous RNAs, which confirms their role in regulating the antiviral response [86, 87].

A comparative analysis of current technologies for specific prevention and treatment of rotavirus infection

This review presents a comparative analysis of the following vaccine platforms: classical live oral vaccines (Rotarix, RotaTeq, etc.); mRNA vaccines, subunit vaccines, and VLP vaccines (Table 1); as well as therapeutic strategies (standard pathogenetic therapy, immunoglobulins, RNA interference) (Table 2).

 

Table 1. A comparative analysis of approaches to Rotavirus treatment and prevention

Parameter	Conventional vaccines	mRNA vaccines	Subunit vaccines	VLP vaccines
Type of technology	Live attenuated viral vaccine (monovalent or polyvalent reassortant)	mRNA encapsulated in LNPs	Recombinant proteins (VP8*, VP7, VP6) with an adjuvant	Virus-like particles assembled from recombinant capsid proteins (VP2/6/7)
Aim of application	Prevention (vaccination of healthy children to prevent disease)	Prevention (vaccination of healthy children to prevent disease)	Prevention (vaccination of healthy children to prevent disease)	Prevention (vaccination of healthy children to prevent disease)
Mechanism of action	Replication followed by antigen presentation The attenuated virus penetrates the enterocytes of the small intestine, where it undergoes a replicative cycle. This leads to the production of viral structural proteins (VP4, VP7, VP6) and non-structural proteins (NSP1–5). Antigens are presented by dendritic cells and macrophages via MHC I and MHC II, inducing a T-cell response and subsequent B-cell activation [51, 88, 89]	Translation of exogenous mRNA The mRNA/LNP complex undergoes endocytosis by APCs. In the cytoplasm, the mRNA is released from the endosome, after which the ribosomes of the APCs translate the target viral protein (e.g., VP7). The protein is processed in the proteasome, and peptides are loaded onto MHC class I, leading to cross-presentation and a CD8+ T-cell response, as well as stimulation of the humoral immune response (Th2) [62, 63, 67]	Recombinant proteins with an adjuvant are taken up by APCs, processed in endosomes, and presented via MHC class II, which activates CD4+ T helper cells and B cells. In contrast, the activation of CD8+ T cells is minimal [93]	VLPs are taken up by macrophages; some are processed via MHC class II (humoral response), while others exit the endosomes and enter the cytosol for presentation via MHC class I. This ensures the simultaneous activation of CD4+ and CD8+ T cells [92]
Effectiveness	High, but variable Existing oral live vaccines effectively reduce the severity of the disease and the need for hospitalization. However, the vaccine is more effective in high-income countries with a high quality of life than in middle- and low-income countries [41]	Potentially high Overcomes the limitations of live vaccines (such as maternal antibody interference). Data from preclinical studies [64, 67]	Low The trivalent candidate TV P2-VP8 did not outperform Rotarix (relative efficacy of 77.68%). Based on the results of the Phase III clinical trial, the study has been discontinued [69]	Potentially high Preclinical studies have confirmed the safety and immunogenicity of the Gam-VLP-rota vaccine [93]. Clinical trials have been successfully completed.
Route of administration	Oral	Injection (intramuscular)	Injection (intramuscular)	Injection (intramuscular)
Scheme of administration	2 or 3 doses depending on the manufacturer: Rotarix: 2 doses (from 6 to 24 weeks);	2–3 doses (a booster shot is required to maintain antibody levels)	2–3 doses	2–3 doses
	RotaTeq: 3 doses (from 6 to 32 weeks); Rota-V-Aid: 3 doses (from 6 to 32 weeks)
Age limitations	Only for infants: First dose: 6–14 weeks; final dose: up to 32 weeks	No restrictions (potentially suitable for all ages, including adults)	No restrictions (potentially suitable for all ages, including adults)	No restrictions (potentially suitable for all ages, including adults)
Thermal stability	From +2°C to +8°C (RotaTeq, Rotarix, ROTASIIL). Shelf life: up to 24 months; 25°C (ROTASIIL Thermo). Shelf life up to 30 months; –20°C (RotAVac). Shelf life up to 5 years; from –25°C to –15°C (Rotavin-M1). Shelf life up to 24 months [90]	Ultralow temperatures from –20°C to –70°C for LNP stability	+2…+8°C	–20°C or +2…+8°C (depending on the formulation)
Key advantages	Proven effectiveness; oral administration; relatively low production cost	Safety (no live virus → no risk of intestinal intussusception); targeted design (rapid development for new strains); overcoming passive immunity (not blocked by maternal antibodies)	Safety (no live virus → no risk of intestinal intussusception); Production in prokaryotic expression systems (E. coli) ensures high yield of the target protein and low cost of the final product; a well-established mechanism for preclinical and clinical evaluation due to the availability of registered subunit vaccines against other pathogens (pertussis, meningococcus, hepatitis B)	Native epitope conformation due to particle self-assembly; dual presentation via MHC I and MHC II with activation of CD4+ and CD8+ T cells; effective antigen-presenting cell (APC) uptake due to optimal particle size (20–200 nm); validated technology platform (HPV, hepatitis B)
Main risks and disadvantages	Risk of intussusception; reduced efficacy in developing countries (interference from the oral poliovirus vaccine and the microbiome); contraindicated in cases of severe combined immunodeficiency; problems with cold-chain transportation [41, 63]	Thermal instability (requires deep-freezing for storage); high cost (LNP technology and synthesis); instability in the gastrointestinal tract	Weak immunogenicity without a potent adjuvant; low efficacy in vivo (based on Phase III data) [71]; predominantly humoral response	The complexity and high cost of production (eukaryotic expression systems); the necessity to optimize the formulation
Current status (2026)	Rotarix, RotaTeq, Rotavac, LLR, Rotavin-M1, and RotaSiil (licensed) are widely used around the world. They are included in the national immunization schedules of more than 100 countries [51]	Development and preclinical studies (in vitro and in vivo) — candidates for rotavirus are being developed	TV P2-VP8 — Phase III completed, trial discontinued [60]. Chinese candidate (Wantai) — Phase I approval (2026)	Gam-VLP-rota (Russia) — clinical trials completed; currently undergoing registration with the Russian Ministry of Health (2026)

 

Table 2. A comparative analysis of approaches to the treatment of Rotavirus infections

Параметр	Standard pathogenetic therapy	Immunoglobulins (IgY antibodies)	RNA interference (siRNA/miRNA)
Type of technology	Oral rehydration, probiotics, enterosorbents	Oral immunoglobulins	RNA interference (siRNA, miRNA, lncRNA) that inhibits viral replication
Aim of application	Therapy (relief of symptoms, correction of fluid and electrolyte balance)	Therapy (passive immunization, neutralization of the virus in the intestinal lumen)	Therapy (treatment of infected or immunocompromised patients)
Mechanism of action	Replacement of fluid and electrolyte losses (rehydration) [48] Modulation of the microbiota and enhancement of mucosal immunity (probiotics) [49, 50] Binding and removal of viral particles, toxins, and gases from the gastrointestinal tract (enterosorbents) [41]	Specific IgY antibodies bind to rotavirus surface proteins (VP4, VP7), blocking viral adsorption to enterocytes and preventing its entry into target cells in the intestine [41]	Synthetized double-stranded small interfering RNAs (siRNAs) are incorporated into the RISC complex. The RISC-bound antisense strand of the siRNA binds complementarily to the target viral mRNA (e.g., the VP6 gene). The Argonaute 2 endonuclease catalyzes the cleavage of viral mRNA, thereby blocking the translation of viral proteins [61–63]
Effectiveness	Confirmed for rehydration (reduction in mortality from diarrheal diseases). Probiotics and enterosorbents—moderate effect (reduction in the duration of diarrhea by 1–2 days) [41, 48–50]	Confirmed Reduction in the duration of diarrhea, reduction in the duration of viral shedding, and enhancement of local immunity [41]	Potentially high Direct inhibition of the virus at the genetic level. Effective against all serotypes when the target is precisely selected [90]
Etiological therapy	None (pathogenetic and symptomatic treatment only)	Yes (direct neutralization of the virus)	Yes (direct inhibition of viral protein synthesis)
Method of administration	Oral (rehydration solutions, probiotics and enterosorbents)	Oral (in capsule or solution form)	Oral (in capsule form)
Age limitations	Without limitations (potentially for all ages, including adults)	Without limitations (potentially for all ages, including adults)	Without limitations (potentially for all ages, including adults)
Thermal stability	Stable at room temperature	IgY antibodies are stable in lyophilized form at +2–8°C	Ultralow temperatures –20°C to –70°C for LNP stability
Key advantages	Availability and low cost; well-established clinical protocols; reduction in disease severity when used in a timely manner	High specificity; safety (no systemic absorption); effectiveness against different genotypes	Etiological treatment; safety for immunocompromised patients; high specificity
Main risks and disadvantages	Lack of etiological effect (the virus is eliminated by the body on its own); ineffectiveness in cases of severe dehydration without intravenous administration	The high cost of producing IgY antibodies; potential degradation in the gastrointestinal tract without a protective coating; requires repeated administration during the acute phase	The difficulty of delivering RNA to the target; the risk of off-target effects; the high cost of synthesis; the short-lived nature of the effect
Current status (2026)	Widely used in clinical practice (WHO recommendations, national protocols)	Clinical trials have been completed; it is currently being used on a limited scale (not included in standard protocols)	Development and preclinical in vitro studies — Candidate vaccines for rotavirus are being developed

 

Conventional live oral vaccines remain the primary tool for mass prevention, despite their shortcomings. mRNA vaccines offer a promising alternative for overcoming the immunological and manufacturing limitations of live vaccines, but require solutions to issues of thermal stability and cost. Subunit vaccines, despite their safety and technological simplicity, have demonstrated low efficacy in clinical trials (TV P2-VP8, Phase III). The platform closest to implementation is VLP vaccines (including the Russian Gam-VLP-rota), which combine the safety of subunit vaccines with high immunogenicity by preserving the native conformation of epitopes.

Standard therapy (rehydration, probiotics, enterosorbents) remains the mainstay of treatment, but it has no etiological effect.

Oral IgY antibodies have demonstrated clinical efficacy, but their application is limited by high cost and the need for multiple doses.

RNA interference (siRNA, miRNA, lncRNA) is the most promising etiological approach capable of directly inhibiting viral replication. It has been shown that transfection of miR-Mimic protective miRNAs (miR-525-3p, miR-194-3p, miR-192/215 family) suppresses viral replication, and the identification of proviral lncRNAs (SLC7A11-AS1) opens up new targets for inhibitors of the infectious process. However, this innovative approach remains in the preclinical stage due to challenges in delivering RNA to enterocytes. RNA therapy is not suitable for mass vaccination but rather for treating severe cases and protecting patients for whom live vaccines are contraindicated (e.g., in severe combined immunodeficiency).

RNA technologies offer fundamentally new possibilities. mRNA vaccines (especially trivalent candidates based on VP8* genotypes P[4], P[6], and P[8] in the LS-P2-VP8* [A1]) demonstrate in preclinical models (mice, guinea pigs, and gnotobiotic piglets) the ability to induce durable humoral and cellular immunity.

This approach overcomes a key limitation of live oral vaccines—maternal antibody interference.

However, mRNA vaccines have not yet been sufficiently tested over time. It is impossible to confirm that there are no drawbacks to the application of mRNA vaccines, as uncontrolled activation of autoimmune processes in the body could lead to the development of complications.

Further research should focus on improving RNA delivery systems, increasing the thermal stability of lipid nanoparticles, enhancing safety, and evaluating the “effectiveness–safety–cost” ratio under real-world epidemiological conditions.

About the authors

Ekaterina V. Torkunova

Institute of Experimental Medicine; Peter the Great St. Petersburg Polytechnic University

Email: torkunova2000@mail.ru
ORCID iD: 0009-0002-2949-8837

junior researcher, Laboratory of immunology and prevention of viral infections, Department of virology and immunology named after academician A.A. Smorodintsev, postgraduate student, laboratory researcher, Immunobiotechnology and Gene Therapy Research Complex, Institute of Biomedical Systems and Biotechnology

Russian Federation, St. Petersburg; St. Petersburg

Tatyana A. Kashina

Institute of Experimental Medicine; Peter the Great St. Petersburg Polytechnic University

Email: tat.kashina@list.ru
ORCID iD: 0000-0001-6687-1720

researcher, Laboratory of lipoproteins named after Academician of the Russian Academy of Medical Sciences A.N. Klimov, Department of molecular biology, genetics and fundamental medicine, postgraduate student, engineer, Graduate School of Biotechnology and Food Production, Institute of Biomedical Systems and Biotechnology

Russian Federation, St. Petersburg; St. Petersburg

Kristina N. Rodionova

Institute of Experimental Medicine

Email: rkn0306@mail.ru
ORCID iD: 0000-0001-6187-2097

postgraduate student, laboratory researcher, Laboratory of immunology and prevention of viral infections, Department of virology and immunology named after academician A.A. Smorodintsev

Russian Federation, St. Petersburg

Victoria A. Matyushenko

Institute of Experimental Medicine

Author for correspondence.
Email: matyshenko@iemspb.ru
ORCID iD: 0000-0002-4698-6085

Cand. Sci. (Biol.), researcher, Laboratory of immunology and prevention of viral infections, Department of virology and immunology named after academician A.A. Smorodintsev

Russian Federation, St. Petersburg

Andrey V. Vasin

Peter the Great St. Petersburg Polytechnic University; Influenza Research Institute named after A.A. Smorodintsev

Email: vasin_av@spbstu.ru
ORCID iD: 0000-0002-1391-7139

Dr. Sci. (Biol.), Professor of the Russian Academy of Sciences, Director, Institute of Biomedical Systems and Biotechnology, Head, Laboratory of molecular biology of viruses

Russian Federation, St. Petersburg; St. Petersburg

Irina N. Isakova-Sivak

Institute of Experimental Medicine

Email: isakova.sivak@iemspb.ru
ORCID iD: 0000-0002-2801-1508

Dr. Sci. (Biol.), Corresponding Member of the Russian Academy of Sciences, Deputy director for scientific work

Russian Federation, St. Petersburg

Aleksandra V. Brodskaia

Peter the Great St. Petersburg Polytechnic University; Influenza Research Institute named after A.A. Smorodintsev

Email: broskaya_av@spbstu.ru
ORCID iD: 0000-0001-5130-3755

Cand. Sci. (Biol.), Associate Professor, Graduate School of Biomedical Systems and Technologies, Director, Immunobiotechnology and Gene Therapy Research Complex, Institute of Biomedical Systems and Biotechnology, senior researcher, Laboratory of intracellular signaling and transport

Russian Federation, St. Petersburg; St. Petersburg

References

Supplementary files