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Bulletin of Mathematical Biology Jun 2024How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains...
How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.
Topics: Measles; Animals; Viremia; Measles virus; Mathematical Concepts; Viral Load; Macaca fascicularis; Likelihood Functions; Humans; Models, Immunological; Models, Biological; T-Lymphocytes; Lymphocyte Activation
PubMed: 38853189
DOI: 10.1007/s11538-024-01305-0 -
Signal Transduction and Targeted Therapy Jun 2024Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific...
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Pyridines; Mice; Animals; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Farnesyltranstransferase; Antiviral Agents; Piperidines; Mice, Inbred BALB C; Protein Conformation; Dibenzocycloheptenes
PubMed: 38853183
DOI: 10.1038/s41392-024-01858-5 -
Human Vaccines & Immunotherapeutics Dec 2024A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups...
A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.
Topics: Humans; Female; Pregnancy; Respiratory Syncytial Virus Infections; United States; Adult; Respiratory Syncytial Virus Vaccines; Latent Class Analysis; Young Adult; Respiratory Syncytial Virus, Human; Infant; Surveys and Questionnaires; Patient Preference; Vaccination; Pregnant Women; Antibodies, Monoclonal; Adolescent
PubMed: 38847198
DOI: 10.1080/21645515.2024.2358566 -
Influenza and Other Respiratory Viruses Jun 2024In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory...
Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.
Topics: Humans; France; Respiratory Syncytial Virus Infections; Infant; Intensive Care Units, Pediatric; Case-Control Studies; Male; Female; Hospitalization; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis; Bronchiolitis, Viral; Treatment Outcome
PubMed: 38840301
DOI: 10.1111/irv.13311 -
Respiratory Research Jun 2024The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology...
BACKGROUND
The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology laboratories. Multiplexed molecular testing on automated platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube is a useful approach for current and future diagnosis of respiratory infections in the clinical setting.
METHODS
Two time periods were included in the study: from February to April 2022, an early 2022 period, during the gradual lifting of COVID-19 prevention measures in the country, and from October 2022 to April 2023, the 2022/23 respiratory infections season. We analysed a total of 1,918 samples in the first period and 18,131 respiratory samples in the second period using a multiplex molecular assay for the simultaneous detection of Influenza A (Flu-A), Influenza B (Flu-B), Human Respiratory Syncytial Virus (HRSV) and SARS-CoV-2.
RESULTS
The results from early 2022 showed a strong dominance of SARS-CoV-2 infections with 1,267/1,918 (66.1%) cases. Flu-A was detected in 30/1,918 (1.6%) samples, HRSV in 14/1,918 (0.7%) samples, and Flu-B in 2/1,918 (0.1%) samples. Flu-A/SARS-CoV-2 co-detections were observed in 11/1,267 (0.9%) samples, and HRSV/SARS-CoV-2 co-detection in 5/1,267 (0.4%) samples. During the 2022/23 winter respiratory season, SARS-CoV-2 was detected in 1,738/18,131 (9.6%), Flu-A in 628/18,131 (3.5%), Flu-B in 106/18,131 (0.6%), and HRSV in 505/18,131 (2.8%) samples. Interestingly, co-detections were present to a similar extent as in early 2022.
CONCLUSION
The results show that the multiplex molecular approach is a valuable tool for the simultaneous laboratory diagnosis of SARS-CoV-2, Flu-A/B, and HRSV in hospitalized and outpatients. Infections with Flu-A/B, and HRSV occurred shortly after the COVID-19 control measures were lifted, so a strong reoccurrence of various respiratory infections and co-detections in the post COVID-19 period was to be expected.
Topics: Humans; COVID-19; Influenza B virus; Influenza, Human; SARS-CoV-2; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Influenza A virus; Male; Female; Coinfection; Middle Aged; Adult; Molecular Diagnostic Techniques; Seasons; Aged
PubMed: 38840154
DOI: 10.1186/s12931-024-02862-7 -
Applied Microbiology and Biotechnology Jun 2024Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to...
Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log (approximately 1.1 log). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.
Topics: Newcastle disease virus; Pilot Projects; Newcastle Disease; Viral Vaccines; Vacuum; Animals; Temperature; Chickens; Desiccation; China; Drug Stability; Viral Load
PubMed: 38836885
DOI: 10.1007/s00253-024-13174-7 -
Mikrochimica Acta Jun 2024A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid...
A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
Topics: Humans; Arachidonic Acid; COVID-19; Biosensing Techniques; SARS-CoV-2; Horseradish Peroxidase; Respiratory Syncytial Viruses; Immunoassay; Streptavidin; Biotin; Limit of Detection
PubMed: 38834823
DOI: 10.1007/s00604-024-06440-y -
Veterinaria Italiana Dec 2023Emerging and re-emerging viral diseases shared between wildlife and domestic animals are continually spreading to new geographic locations, influenced by human...
Emerging and re-emerging viral diseases shared between wildlife and domestic animals are continually spreading to new geographic locations, influenced by human activities and environmental change. Canine distemper (CD) is probably one of the best examples of a disease that has been proved to be capable of compromising the conservation of several wild carnivore species. In this article, we describe a case report of CD in a grey wolf (Canis lupus) in Iran. A grey wolf was found in Fars Province close to Bamou national park. Clinical signs were characterized by neurologic signs, muscle twitching, hyperkeratosis of the footpads and nose and keratoconjunctivitis sicca. After the death of the animal, samples were taken from different organs and sent to collaborator laboratory of Fars Provincial Office of Veterinary Organization. RT-PCR assays confirmed canine distemper virus in the grey wolf. This is the first documented report of canine distemper virus in wild species from Fars Province of Iran.
Topics: Animals; Iran; Wolves; Distemper Virus, Canine; Distemper; Male
PubMed: 38828858
DOI: 10.12834/VetIt.3067.20864.2 -
Archives of Razi Institute Dec 2023Aluminum-containing adjuvants are extensively used in inactive human and animal vaccines owing to their favorable immunostimulatory and safe properties. Nonetheless,... (Comparative Study)
Comparative Study
A Comparative Study of the Effects of Al(OH) and AlPO Adjuvants on the Production of Neutralizing Antibodies (NAbs) against Bovine parainfluenza Virus Type 3 (BPIV3) in Guinea Pigs.
Aluminum-containing adjuvants are extensively used in inactive human and animal vaccines owing to their favorable immunostimulatory and safe properties. Nonetheless, there is controversy over the effects of different aluminum salts as an adjuvant for the bovine parainfluenza virus type 3 (BPIV3) vaccine. In order to find a suitable adjuvant, we studied the effects of two adjuvants (i.e., aluminum hydroxide [Al(OH)] and aluminum potassium sulfate [AlPO]) on the production of neutralizing antibodies (NAbs) for an experimental BPIV3 vaccine. The animals under study (Guinea pigs) were randomly assigned to five groups of experimental vaccines containing Al(OH) (AH), AlPO (AP), Al(OH)-AlPO mixture (MIX), commercial vaccine (COM), and control (NS). The treatment groups were immunized with two doses of vaccine 21 days apart (on days 0 and 21), and the control group received normal saline under the same conditions. The animals were monitored for 42 days, and blood samples were then taken. The results indicated that all vaccines were able to induce the production of NAbs at levels higher than the minimum protective titer (0.6). An increase in titer was observed throughout the monitoring period. Moreover, an increase in both the level and mean titer of NAbs obtained from the vaccine containing Al(OH) adjuvant was significantly higher than in the other studied groups (P≤0.005). The comparison of NAbs titer in other groups did not display a significant difference. Considering the speed of rising and the optimal titer of NAbs production in the experimental vaccine, the Al(OH) adjuvant is a suitable candidate for preparing a vaccine against BPIV3 for immunization.
Topics: Animals; Adjuvants, Immunologic; Aluminum Hydroxide; Antibodies, Neutralizing; Guinea Pigs; Parainfluenza Virus 3, Bovine; Viral Vaccines; Antibodies, Viral; Random Allocation; Aluminum Compounds; Female
PubMed: 38828184
DOI: 10.32592/ARI.2023.78.6.1779 -
Archives of Razi Institute Dec 2023Newcastle disease (ND) is an economically significant and extremely spreadable viral illness affecting a wide variety of avian species. ND can rapidly spread within...
Newcastle disease (ND) is an economically significant and extremely spreadable viral illness affecting a wide variety of avian species. ND can rapidly spread within poultry farms and result in considerable economic losses for the global poultry industry. This disease is endemic in Iran, and despite intensive vaccination efforts in the poultry industry, outbreaks of ND occur unexpectedly. This study aimed to isolate the Newcastle disease virus (NDV) from poultry farms with breathing problems in Markazi province, Iran, and investigate the evolutionary relationship and molecular characteristics of the isolates during 2017-2019. To this end, tissue samples (lung, brain, and trachea) were taken from 42 broiler farms exhibiting respiratory symptoms. The samples were inoculated into 9-11-day-old embryonated eggs, and the virus was isolated from 20 (47.6%) of the 42 farms. Subsequently, RT-PCR was used to amplify partial fusion gene sequences from the new isolates. The amplified products were sequenced and compared phylogenetically to the standard pilot dataset (125 selected sequences) generated by the NDV consortium. As determined by phylogenetic analysis, all nine isolates belonged to subgenotype VII.1.1 of genotype VII and were highly similar to isolates from other parts of Iran and China. Moreover, all isolates possessed a polybasic cleavage site motif (112RRQKRF117), characteristic of virulent strains. Furthermore, the present isolates shared a high nucleotide identity (96%) with viruses previously isolated from other provinces of Iran, as determined by BLAST searches and multiple alignments. In addition, they shared a high degree of sequence similarity but were distinct from the existing NDV vaccines. Therefore, the genetic dissimilarity between current vaccine strains and circulating NDVs must be considered in vaccination programs.
Topics: Animals; Iran; Newcastle disease virus; Newcastle Disease; Chickens; Poultry Diseases; Phylogeny; Viral Fusion Proteins; Genotype
PubMed: 38828167
DOI: 10.32592/ARI.2023.78.6.1794