Protein Of Respiratory Syncytial Virus Research Articles

A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017-2021

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infection (ALRTI) in children under five years of age. Between 2017 and 2021, 396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China. In addition, 151 sequences from China were sourced from GenBank and GISAID, making a total of 549 RSV F gene sequences subjected to analysis. Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved, although some amino acids (AAs) have undergone changes. AA mutations with frequencies ≥ 10% were identified at six sites and the p27 region: V384I (site I), N276S (site II), R213S (site Ø), and K124N (p27) for RSV A; F45L (site I), M152I/L172Q/S173L/I185V/K191R (site V), and R202Q/I206M/Q209R (site Ø) for RSV B. Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A, while the K191R, I206M, and Q209R frequencies increased by over 10% in RSV B. Notably, the nirsevimab-resistant mutation, S211N in RSV B, increased in frequency from 0% to 1.15%. Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations, with low root-mean-square deviation values. These results could provide foundational data from China for the development of RSV mAbs and vaccines.

Star-shaped flexible arm multivalent aptamers for largely improved virus binding affinity

Here we explore the click chemistry-based synthesis of high affinity multivalent aptamers and their application for virus detection. In contrast to attempts based on rigid constructs, such as aptamer-modified nanoparticles or hybridization-connected constructs, we propose highly flexible “star-shaped” multivalent aptamers to facilitate the cooperative binding to randomly distributed viral proteins on the surface of pleomorphic viruses such as the respiratory syncytial virus (RSV). Polyethylene glycols (PEGs) with 4 azide terminated flexible arms spanning from a pentaerythritol core were conjugated to aptamer strands with dibenzocyclooctyne and a fluorescent label at their, 3’ and 5’ terminus, respectively. By controlling the aptamer - PEG ratio and following electrophoretic separation all the different valency aptamer conjugates could be prepared. For proof of concept, we used an aptamer selected for the G protein of RSV. We show that significantly higher apparent affinities can be obtained by using multivalent aptamers for both the G protein and RSV virus than with the single stranded aptamer, i.e. with up to ca. 2 orders of magnitude. The inherent convenience of synthesizing fluorescently labelled multivalent aptamers leads to a versatile class of affinity ligands for sensing as demonstrated through the improved detection sensitivity of tetravalent aptamer tagged RSV by fluorescence nanoparticle tracking analysis.

The Central Conserved Peptides of Respiratory Syncytial Virus G Protein Enhance the Immune Response to the RSV F Protein in an Adenovirus Vector Vaccine Candidate.

Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines.

Differential expression of cytokines and elevated levels of MALAT1 - Long non-coding RNA in response to non-structural proteins of human respiratory syncytial virus

Human Respiratory Syncytial Virus (hRSV), a prevalent respiratory pathogen affecting various age groups, can trigger prolonged and intense inflammation in humans. The severity and outcome of hRSV infection correlate with elevated levels of pro-inflammatory agents, yet the underlying reasons for this immune system overstimulation remain elusive. We focused on the impact of hRSV non-structural proteins, NS1 and NS2, on immune response within epithelial cells. Available data indicates that these proteins impair the interferon pathway. We reinforce that NS1 and NS2 induce heightened secretion of the pro-inflammatory cytokines IL-6 and CXCL8. We also indicate that hRSV non-structural proteins provoke differential gene expression of human host FosB and long non-coding RNAs (MALAT1, RP11-510N19.5). It suggests an impact of NS molecules beyond IFN pathways. Thus, new light is shed on the interplay between hRSV and host cells, uncovering unexplored avenues of viral interference, especially the NS2 role in cytokine expression and immune modulation.

Impact of COVID-19 Pandemic Restrictions on Respiratory Virus Patterns: Insights from RSV Surveillance in Gwangju, South Korea.

The social restriction measures implemented due to the COVID-19 pandemic have impacted the pattern of occurrences of respiratory viruses. According to surveillance results in the Gwangju region of South Korea, respiratory syncytial virus (RSV) did not occur during the 2020/2021 season. However, there was a delayed resurgence in the 2021/2022 season, peaking until January 2022. To analyze this, a total of 474 RSV positive samples were investigated before and after the COVID-19 pandemic. Among them, 73 samples were selected for whole-genome sequencing. The incidence rate of RSV in the 2021/2022 season after COVID-19 was found to be approximately three-fold higher compared to before the pandemic, with a significant increase observed in the age group from under 2 years old to under 5 years old. Phylogenetic analysis revealed that, for RSV-A, whereas four lineages were observed before COVID-19, only the A.D.3.1 lineage was observed during the 2021/2022 season post-pandemic. Additionally, during the 2022/2023 season, the A.D.1, A.D.3, and A.D.3.1 lineages co-circulated. For RSV-B, while the B.D.4.1.1 lineage existed before COVID-19, both the B.D.4.1.1 and B.D.E.1 lineages circulated after the pandemic. Although atypical RSV occurrences were not due to new lineages, there was an increase in the frequency of mutations in the F protein of RSV after COVID-19. These findings highlight the need to continue monitoring changes in RSV occurrence patterns in the aftermath of the COVID-19 pandemic to develop and manage strategies in response.

Preparation of a mouse monoclonal antibody against the NS1 protein of respiratory syncytial virus

The aim of this study was to prepare a mouse monoclonal antibody against the nonstructural protein 1 (NS1) of respiratory syncytial virus (RSV) to analyze its expression and distribution during transfection and infection. Additionally, we aimed to evaluate the antibody's application in immunoprecipitation assay. Firstly, the NS1 gene fragment was cloned into a prokaryotic plasmid and expressed in Escherichia coli. The resulting NS1 protein was then purified by affinity chromatography, and used to immunize the BALB/c mice. Subsequently, hybridoma cells capable of stably secreting the NS1 monoclonal antibody were selected using indirect enzyme linked immunosorbent assay (ELISA). This monoclonal antibody was employed in both indirect immunofluorescence assay (IFA) and Western blotting to analyze the expression and distribution of RSV NS1 in overexpressed and infected cells. Finally, the reliability of this monoclonal antibody was evaluated through the immunoprecipitation assay. The results showed that the RSV NS1 protein was successfully expressed and purified. Following immunization of mice with this protein, we obtained a highly specific RSV NS1 monoclonal antibody, which belonged to the IgG1 subtype with an antibody titer of 1:15 360 000. Using this monoclonal antibody, the RSV NS1 protein was identified in both transfected and infected cells. The IFA results revealed predominant distribution of NS1 in the cytoplasm and nucleus. Moreover, we confirmed that this monoclonal antibody could effectively bind specifically to NS1 protein in cell lysates, making it suitable as a capture antibody in immunoprecipitation assay. In conclusion, our study successfully achieved production of the RSV NS1 protein through a prokaryotic expression system and prepared a specific monoclonal antibody against NS1. This antibody demonstrates the ability to specifically identify the NS1 protein and can be used in the immunoprecipitation assay, thereby laying a foundation for the functional studies of the NS1 protein.

Wastewater surveillance together with metaviromic data revealed the unusual resurgence of infectious diseases after the first wave of the COVID-19 outbreak

How to address public health priorities after COVID-19 is becoming a critical task. To this end, we conducted wastewater surveillance for six leading pathogens, namely, SARS-CoV-2, norovirus, rotavirus, influenza A virus (IAV), enteroviruses and respiratory syncytial virus (RSV), in Nanchang city from January to April 2023. Metaviromic sequencing was conducted at the 1st, 4th, 7th, 9th, 12th and 14th weeks to reveal the dynamics of viral pathogens that were not covered by qPCR. Amplicon sequencing of the conserved region of norovirus GI and GII and the rotavirus and region encoding nonstructural protein of RSV was also conducted weekly. The results showed that after a rapid decrease in SARS-CoV-2 sewage concentrations occurred in January 2023, surges of norovirus, rotavirus, IAV and RSV started at the 6th, 7th, 8th and 11th weeks, respectively. The dynamics of the sewage concentrations of norovirus, rotavirus, IAV and RSV were consistent with the off-season resurgence of the above infectious diseases. Notably, peak sewage concentrations of norovirus GI, GII, rotavirus, IAV and RSV were found at the 6th, 3rd, 7th, 7th and 8th weeks, respectively. Astroviruses also resurge after the 7th week, as revealed by metaviromic data, suggesting that wastewater surveillance together with metaviromic data provides an essential early warning tool for revealing patterns of infectious disease resurgence.

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

All Eyes on the Prefusion-Stabilized F Construct, but Are We Missing the Potential of Alternative Targets for Respiratory Syncytial Virus Vaccine Design?

Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape of vaccine candidates. Notably, two vaccines targeting the elderly and the first maternal vaccine have recently been approved. The majority of the vaccines and vaccine candidates rely solely on a prefusion-stabilized conformation known for its highly neutralizing epitopes. Although, so far, this antigen design appears to be successful for the elderly, our current understanding remains incomplete, requiring further improvement and refinement in this field. Pediatric vaccines still have a long journey ahead, and we must ensure that vaccines currently entering the market do not lose efficacy due to the emergence of mutations in RSV's circulating strains. This review will provide an overview of the current status of vaccine designs and what to focus on in the future. Further research into antigen design is essential, including the exploration of the potential of alternative RSV proteins to address these challenges and pave the way for the development of novel and effective vaccines, especially in the pediatric population.

Molecular epidemiology and clinical characteristics of respiratory syncytial virus in hospitalized children during winter 2021-2022 in Bengbu, China.

This study aimed to study the molecular epidemiology and clinical characteristics of respiratory syncytial virus (RSV) infection from hospitalized children with ARTI in Bengbu. One hundred twenty-four nasopharyngeal swab specimens and clinical data from children with ARTI cases were collected in Bengbu, China, during winter 2021-2022. The samples were detected by qPCR of 13 respiratory viruses. Phylogenetic analysis was constructed using MEGA 7.0. All analyses were performed using SAS software, version 9.4. In winter 2021-2022, URTI, NSCAP, SCAP, and bronchiolitis accounted for 41.03%, 27.35%, 17.09%, and 14.53% of hospitalized children in Bengbu, China. The detection rates of the top three were RSV (41.94%), ADV (5.65%), and FluB (5.65%) in hospitalized children through 13 virus detection. RSV is the main pathogen of hospitalized children under 2 years old. Forty-eight sequences of G protein of RSV were obtained through PCR amplification, including RSV-A 37 strains and RSV-B 11 strains. Phylogenetic analysis showed that all RSV-A and RSV-B were ON1 and BA9 genotypes, respectively. ON1 genotypes were further divided into two clades. The majority of ON1 strains formed a unique genetic clade with T113I, V131D, N178 G, and H258Q mutations. Furthermore, RSV infection was an independent risk factor for ventilator use (OR = 9.55, 95% CI 1.87-48.64). There was a high incidence of RSV among hospitalized children during winter 2021-2022 in Bengbu with ON1 and BA9 being the dominant strains. This study demonstrated the molecular epidemiological characteristics of RSV in children with respiratory infections in Bengbu, China.

Antiviral effect of alkaloids-free Ephedra Herb extract on respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children. Despite decades of efforts, no effective therapies are available. We recently reported that extracts of Ephedra Herb and Cinnamon Bark interacted with the G attachment protein of RSV to inhibit infectivity. The present in vitro study aimed to investigate the antiviral effect of ephedrine alkaloids-free Ephedra Herb extract (EFE), which is characterized by free of harmful effects of ephedrine alkaloids in Ephedra Herb, on experimental RSV infection. Infection of RSV into A549 cells simultaneously with EFE resulted the significant reduction of RSV RNA, viral protein, and viral titers after the incubation of the cells. We found that RSV attachment to the cell surface was inhibited both in the presence of EFE and when RSV particles were pre-treated with EFE. We also found that EFE specifically interacted with the central conserved domain of RSV G protein by surface plasmon resonance, demonstrating that specific binding of G protein to the cellular receptor was inhibited by EFE. Another mechanism was found in which a higher concentration of EFE inhibited the viral load immediately after the viral entry into host cells, suggesting the inhibition of viral RNA replication. These results demonstrate that EFE worked against RSV infection through multiple antiviral mechanisms, a unique feature of this crude drug extract.

Respiratory Syncytial Virus: Transmission and Treatment

Respiratory Syncytial Virus (RSV), a respiratory tract infection-causing virus with a global distribution and seasonal occurrence, is the second leading cause of death in children under one year old, after malaria. The Respiratory Syncytial virus is an enveloped negative-strand RNA virus from the Paramyxoviridae family primarily transmitted by droplets of a cough or sneeze. However, kisses between infected and healthy individuals can also rapidly spread the virus, especially among children. Typically, the virus causes symptoms such as coughing, sneezing, or a fever making it visibly like other infections or conditions. Young children may have apnea and overall be irritable. Confirmation of RSV diagnosis can be done through available RSV-card tests or through RT-PCR tests. Though there is no standard treatment for RSV infection, drugs such as Ribavirin and Synagis (Palivizumab) are currently used for managing symptoms of RSV infection in areas that have access to such medications. Palivizumab is used to treat prophylaxis, the prevention of serious lower respiratory tract disease brought on by RSV in children at high risk of RSV disease, is the greatest preventative approach. Numerous clinical studies are being conducted right now to treat and prevent RSV infection. Most of the study focuses on children below the age of 5 years because they are the most vulnerable, but there is also research on the prevalence of RSV in older adults and the effects of maternal vaccination on infants through the antibodies made to fight against RSV infection. G protein, F protein, and SH protein are three crucial membrane proteins that make up the RSV structure. A vaccine containing both the F and G RSV proteins would offer more protection against RSV. The F and G protein stimulates antibody formation, which neutralizes the virus. The RSV treatment plans and vaccine trials within India, South Africa, the United States of America, and the United Kingdom show similarities and differences that could be utilized to develop a treatment plan for RSV. In the upcoming years, further research is required to produce a cheaper alternative that is accessible to all countries. This will help to establish a set, effective protocol for RSV to be used worldwide.

Inhibition of respiratory syncytial virus by Daclatasvir and its derivatives: synthesis of computational derivatives as a new drug development

The most common cause of respiratory tract illness in newborns and young children is the respiratory syncytial virus (RSV). There is no approved vaccination or specific antiviral medication for RSV infections. Here, an attempt has been made to explore the potential of currently marketed drugs as well as their probable derivatives to improve the possibility of developing stronger medications against RSV. From the 100 synthetic drug compounds library, the best drug molecule was identified through drug-likeness properties, toxicity, molecular docking and molecular dynamics simulations. Molecular Mechanics Generalized Born Surface Area (MM-GBSA) was also a method that was applied in this study. Daclatasvir showed the highest binding energy and appeared as the best drug to inhibit matrix protein and a fusion protein of RSV. Based on Daclatasvir, 40 computational derivatives were made. D28, D34 and D40 showed far better results than the actual drug. Changes in lipophilicity character increase the binding energy of derivatives. Molecular dynamic simulations showed their non-deviated, non-fluctuated and stable complex formation with target proteins. The high number of amino acid contacts throughout the trajectory increases the stability and effectiveness of derivatives. The key to producing a novel medicine to eradicate RSV is provided by derivatives. Daclatasvir will be employed as a potential RSV inhibitor up until that point. Communicated by Ramaswamy H. Sarma

Effect of Palivizumab Prophylaxis on Respiratory Syncytial Virus Infection in Very Preterm Infants in the First Year of Life in The Netherlands.

Respiratory Syncytial Virus (RSV) poses a severe threat to infants, particularly preterm infants. Palivizumab, the standard preventive prophylaxis, is primarily utilized in high-risk newborns due to its cost. This study assessed palivizumab's effectiveness in preventing RSV infections in predominantly very preterm infants during their first year of life. Serum samples from a prospective multicentre cohort study in the Netherlands were analyzed to assess RSV infection rates by measuring IgG levels against three RSV proteins: nucleoprotein, pre-fusion, and post-fusion protein. Infants were stratified based on gestational age (GA), distinguishing very preterm (≤32 weeks GA) from moderate/late preterm (>32 to ≤36 weeks GA). In very preterm infants, palivizumab prophylaxis significantly reduced infection rates (18.9% vs. 48.3% in the prophylaxis vs. non-prophylaxis group. Accounting for GA, sex, birth season, and birth weight, the prophylaxis group showed significantly lower infection odds. In infants with >32 to ≤36 weeks GA, the non-prophylaxis group (55.4%) showed infection rates similar to the non-prophylaxis ≤32-week GA group, despite higher maternal antibody levels in the moderate/late preterm infants. In conclusion, palivizumab prophylaxis significantly reduces RSV infection rates in very premature infants. Future research should explore clinical implications and reasons for non-compliance, and compare palivizumab with emerging prophylactics like nirsevimab aiming to optimize RSV prophylaxis and improve preterm infant outcomes.

The nonstructural protein 1 of respiratory syncytial virus hijacks host mitophagy as a novel mitophagy receptor to evade the type I IFN response in HEp-2 cells.

It is a worthy concern for us to understand virus-host interactions which affect progression and prognosis of disease. We demonstrated that the non-structural protein 1 of respiratory syncytial virus (RSV NS1) may act as a novel mitophagy receptor to induce mitophagy by binding LC3B and mitochondrial protein TUFM, and finally dampen interferon (IFN) responses induced by RIG1 and RSV infection. TUFM is beneficial for RSV replication in vivo and vitro. It is new and interesting that RSV NS1 may function as a mitophagy receptor to interact with LC3B. The LIR motif of NS1 protein is essential for its interaction with LC3B. We further confirm that RSV NS1 inhibited IFNβ response and promoted RSV replication in autophagy-dependent mechanisms in vivo and vitro. Our study contributes to understanding virus-host interaction, enriching our insights into RSV pathogenic mechanism and exploiting new antiviral treatments targeting TUFM.

Rapid and simultaneous multiple detection of a tripledemic using a dual-gate oxide semiconductor thin-film transistor-based immunosensor

The simultaneous infection with a tripledemic—simultaneous infection with influenza A pH1N1 virus (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV)—necessitates the development of accurate and fast multiplex diagnostic tests. The coronavirus disease 2019 (COVID-19) pandemic has emphasized the importance of virus detection. Field-effect transistor (FET)-based immuno-biosensors have a short detection time and do not require labeling or polymerase chain reaction. This study demonstrates the rapid, sensitive detection of influenza A pH1N1, SARS-CoV-2, and RSV using a multiplex immunosensor based on a dual-gate oxide semiconductor thin-film transistor (TFT), a type of FET. The dual-gate oxide TFT was modified by adjusting both top and bottom gate insulators to improve capacitive coupling to approximately 120-fold amplification, exhibiting a high pH sensitivity of about 10 V/pH. The dual-gate oxide TFT-based immunosensor detected the target proteins (hemagglutinin (HA) protein of Flu, spike 1 (S1) protein of SARS-CoV-2, and fusion protein of RSV) of each virus, with a limit of detection of approximately 1 fg/mL. Cultured viruses in phosphate-buffered saline or artificial saliva and clinical nasopharynx samples were detected in 1-μL sample volumes within 60 s. This promising diagnosis could be potentially as point-of-care tests to facilitate a prompt response to future pandemics with high sensitivity and multiplexed detection without pretreatment.

The matrix protein of respiratory syncytial virus suppresses interferon signaling via RACK1 association.

Respiratory syncytial virus (RSV) matrix (M) protein is indispensable for virion assembly and release. It is localized to the nucleus during early infection to perturb host transcription. However, the function of RSV M protein in other cellular activities remains poorly understood. In this study, several interferon response-associated host factors, including RACK1, were identified by proteomic analysis as RSV M interactors. Knockdown of RACK1 attenuates RSV-restricted IFN signaling leading to enhanced host defense against RSV infection, unraveling a role of M protein in antagonizing IFN response via association with RACK1. Our study uncovers a previously unrecognized mechanism of immune evasion by RSV M protein and identifies RACK1 as a novel host factor recruited by RSV, highlighting RACK1 as a potential new target for RSV therapeutics development.

Identification and Study of the Action Mechanism of Small Compound That Inhibits Replication of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is known to cause annual epidemics of respiratory infections; however, the lack of specific treatment options for this disease poses a challenge. In light of this, there has been a concerted effort to identify small molecules that can effectively combat RSV. This article focuses on the mechanism of action of compound K142, which was identified as a primary screening leader in the earlier stages of the project. The research conducted demonstrates that K142 significantly reduces the intensity of virus penetration into the cells, as well as the formation of syncytia from infected cells. These findings show that the compound's interaction with the surface proteins of RSV is a key factor in its antiviral activity. Furthermore, pharmacological modeling supports that K142 effectively interacts with the F-protein. However, in vivo studies have shown only weak antiviral activity against RSV infection, with a slight decrease in viral load observed in lung tissues. As a result, there is a need to enhance the bioavailability or antiviral properties of this compound. Based on these findings, we hypothesize that further modifications of the compound under study could potentially increase its antiviral activity.

Dynamics of the immune response in laboratory animals to the introduction of a protective protein of the cause of respiratory syncytial infection in cattle

The authors in the article presented the results of assessing the immune response of guinea pigs using the protective protein of the bovine respiratory syncytial infection virus (RSI), obtained using recombinant E. coli BRSV-F1. The research was carried out in the branch laboratory of veterinary biotechnology and infectious animal diseases of the Vitebsk Order of the Badge of Honor of the State Academy of Veterinary Medicine. The average titer of specific antibodies of guinea pigs to the use of the protective protein of the bovine RSI virus was studied in 9 experimental groups and one control group. Blood sampling was carried out at the beginning of the experiment, before the second immunisation and 14 days after the second immunisation. The average titer of specific antibodies to the use of the protective protein of the bovine RSI virus was determined using an indirect hemagglutination reaction with an erythrocyte diagnosticum containing the bovine respiratory syncytial virus (RSV). With the introduction of samples of the prototype vaccine containing the gene encoding the production of the bovine RSI virus protein: group 1 - whole bacteria E. coli BRSV-F1 with an inducer of protein synthesis IPTG; 2nd, whole bacteria E. coli BRSV-F1 with protein synthesis inducer IPTG + 15% adjuvant IZA-15; 3rd, bacterial lysate E. coli BRSV-F1 with an inducer of protein synthesis IPTG; 4th – E. coli bacterial lysate BRSV-F1 with protein synthesis inducer IPTG + 15% adjuvant IZA-15; 5th - protective protein F1 + 15% adjuvant IZA-15; 6th - protective protein F1 + 2% cellulose, 7th - inactivated bovine RSV (JSC «Belvitunipharm») + 15% adjuvant IZA15; 8th - Hiprabovis 4 vaccines (HIPRA, Spain) and 9th - Bovi-shield Gold FP 5 L5 vaccines (Zoetis, USA) - in the experimental groups, an increase in antibody titer in paired blood sera was noted compared to the control group. From the data obtained, it was concluded that the studied samples of the vaccine prototype containing the gene encoding the production of the bovine RSV protein are not inferior in immunogenic activity to the vaccines Bovishield Gold FP 5 L5 and Hiprabovis 4. Therefore, the protective protein of the bovine RSI virus can be included in the composition of vaccines against this pathology to replace the cultural virus.

Cationic-nanogel nasal vaccine containing the ectodomain of RSV-small hydrophobic protein induces protective immunity in rodents.

Respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection, especially in children and the elderly. Various vaccines containing the major transmembrane surface proteins of RSV (proteins F and G) have been tested; however, they have either afforded inadequate protection or are associated with the risk of vaccine-enhanced disease (VED). Recently, F protein-based maternal immunization and vaccines for elderly patients have shown promising results in phase III clinical trials, however, these vaccines have been administered by injection. Here, we examined the potential of using the ectodomain of small hydrophobic protein (SHe), also an RSV transmembrane surface protein, as a nasal vaccine antigen. A vaccine was formulated using our previously developed cationic cholesteryl-group-bearing pullulan nanogel as the delivery system, and SHe was linked in triplicate to pneumococcal surface protein A as a carrier protein. Nasal immunization of mice and cotton rats induced both SHe-specific serum IgG and mucosal IgA antibodies, preventing viral invasion in both the upper and lower respiratory tracts without inducing VED. Moreover, nasal immunization induced greater protective immunity against RSV in the upper respiratory tract than did systemic immunization, suggesting a critical role for mucosal RSV-specific IgA responses in viral elimination at the airway epithelium. Thus, our nasal vaccine induced effective protection against RSV infection in the airway mucosa and is therefore a promising vaccine candidate for further development.