scholarly journals Brief on Recent Application of Liposomal Vaccines for Lower Respiratory Tract Viral Infections: From Influenza to COVID-19 Vaccines

2021 ◽  
Vol 14 (11) ◽  
pp. 1173
Author(s):  
Mohamed Ahmed Attia ◽  
Ebtessam Ahmed Essa ◽  
Toka Tarek Elebyary ◽  
Ahmed Mostafa Faheem ◽  
Amal Ali Elkordy
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Viral Infections ◽  
Vaccine Development ◽  
Effective Means ◽  
Great Success ◽  
Lipophilic Compounds ◽  
Vesicular Structure ◽  
Common Causes ◽  
Syncytial Virus

Vaccination is the most effective means of preventing infectious diseases and saving lives. Modern biotechnology largely enabled vaccine development. In the meantime, recent advances in pharmaceutical technology have resulted in the emergence of nanoparticles that are extensively investigated as promising miniaturized drug delivery systems. Scientists are particularly interested in liposomes as an important carrier for vaccine development. Wide acceptability of liposomes lies in their flexibility and versatility. Due to their unique vesicular structure with alternating aqueous and lipid compartments, liposomes can enclose both hydrophilic and lipophilic compounds, including antigens. Liposome composition can be tailored to obtain the desired immune response and adjuvant characteristics. During the current pandemic of COVID-19, many liposome-based vaccines have been developed with great success. This review covers a liposome-based vaccine designed particularly to combat viral infection of the lower respiratory tract (LRT), i.e., infection of the lung, specifically in the lower airways. Viruses such as influenza, respiratory syncytial virus (RSV), severe acute respiratory syndrome (SARS-CoV-1 and SARS-CoV-2) are common causes of LRT infections, hence this review mainly focuses on this category of viruses.

scholarly journals MTOR Kinase is a Therapeutic Target for Respiratory Syncytial Virus and Coronaviruses

2021 ◽  
Author(s):  
HoangDinh Huynh ◽  
Ruth Levitz ◽  
Jeffrey Kahn
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Protein Production ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Effective Means ◽  
Therapeutic Interventions ◽  
Respiratory Pathogen ◽  
Upper Respiratory Tract ◽  
Syncytial Virus

Abstract Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as targeting host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, limits RSV protein production and viral replication. Further, we show that this approach is generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, protein production and replication. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particular in the absence of antiviral drugs.

scholarly journals mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
HoangDinh Huynh ◽  
Ruth Levitz ◽  
Rong Huang ◽  
Jeffrey S. Kahn
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Protein Production ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Effective Means ◽  
Respiratory Pathogen ◽  
Progeny Virus ◽  
Upper Respiratory Tract ◽  
Syncytial Virus

AbstractTherapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.

scholarly journals The long road to protect infants against severe RSV lower respiratory tract illness

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 610 ◽  
Author(s):  
Sofia Jares Baglivo ◽  
Fernando P Polack
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Vaccine Development ◽  
The Elderly ◽  
Recurrent Wheezing ◽  
Maternal Immunization ◽  
Current Vaccine ◽  
History Of ◽  
Respiratory Tract Illness ◽  
Syncytial Virus

Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies.

scholarly journals Modelling hospital admissions for lower respiratory tract infections in the elderly in England

2006 ◽  
Vol 134 (6) ◽  
pp. 1150-1157 ◽  
Author(s):  
B. MÜLLER-PEBODY ◽  
N. S. CROWCROFT ◽  
M. C. ZAMBON ◽  
W. J. EDMUNDS
Keyword(s):  
Respiratory Tract ◽  
Elderly Patients ◽  
Lower Respiratory Tract ◽  
Hospital Admissions ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Linear Regression Analysis ◽  
Respiratory Pathogens ◽  
Syncytial Virus ◽  
Tract Infections

Despite the importance of lower respiratory-tract infection (LRI) in causing hospitalizations in elderly patients ([ges ]65 years of age) and recent advances in vaccine development, a complete picture of the causative organisms is not available. All hospital discharge diagnoses (ICD-10 code) for LRI in elderly patients in England during 1995–1998 were reviewed. Using known seasonality in potential causative agents of LRI, the contribution of different respiratory pathogens to hospitalizations coded as ‘unspecified LRI’ was estimated by multiple linear regression analysis. Ninety-seven per cent of 551633 LRI-associated diagnoses had no specific organism recorded. From the statistical model the estimated proportions of admissions attributable to different pathogens were applied to calculate estimated hospitalization rates: 93·9 hospitalizations/10000 population aged [ges ]65 years due to S. pneumoniae, 22·9 to influenza virus, 22·3 to H. influenzae, 17·0 to whooping cough, and 12·8 to respiratory syncytial virus. There is enormous potential to improve health using existing vaccines and those under development.

scholarly journals Functional profiling of COVID-19 respiratory tract microbiomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Niina Haiminen ◽  
Filippo Utro ◽  
Ed Seabolt ◽  
Laxmi Parida
Keyword(s):  
Respiratory Tract ◽  
Carbohydrate Metabolism ◽  
Lower Respiratory Tract ◽  
Viral Infections ◽  
Lavage Fluid ◽  
Degradation Pathway ◽  
Community Acquired Pneumonia ◽  
The Body ◽  
Sequencing Data ◽  
Functional Profiling

AbstractIn response to the ongoing global pandemic, characterizing the molecular-level host interactions of the new coronavirus SARS-CoV-2 responsible for COVID-19 has been at the center of unprecedented scientific focus. However, when the virus enters the body it also interacts with the micro-organisms already inhabiting the host. Understanding the virus-host-microbiome interactions can yield additional insights into the biological processes perturbed by viral invasion. Alterations in the gut microbiome species and metabolites have been noted during respiratory viral infections, possibly impacting the lungs via gut-lung microbiome crosstalk. To better characterize microbial functions in the lower respiratory tract during COVID-19 infection, we carry out a functional analysis of previously published metatranscriptome sequencing data of bronchoalveolar lavage fluid from eight COVID-19 cases, twenty-five community-acquired pneumonia patients, and twenty healthy controls. The functional profiles resulting from comparing the sequences against annotated microbial protein domains clearly separate the cohorts. By examining the associated metabolic pathways, distinguishing functional signatures in COVID-19 respiratory tract microbiomes are identified, including decreased potential for lipid metabolism and glycan biosynthesis and metabolism pathways, and increased potential for carbohydrate metabolism pathways. The results include overlap between previous studies on COVID-19 microbiomes, including decrease in the glycosaminoglycan degradation pathway and increase in carbohydrate metabolism. The results also suggest novel connections to consider, possibly specific to the lower respiratory tract microbiome, calling for further research on microbial functions and host-microbiome interactions during SARS-CoV-2 infection.

scholarly journals In SilicoApproach towards Designing Virtual Oligopeptides for HRSV

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ruchi Jain ◽  
Shanmughavel Piramanayagam
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Virus Replication ◽  
Lower Respiratory Tract ◽  
Specific Interaction ◽  
Infection Process ◽  
Rational Choices ◽  
Respiratory Tract Illness ◽  
Syncytial Virus ◽  
Infants And Young Children

HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study,in silicodocking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs.

scholarly journals Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng Lei ◽  
Lisong Yang ◽  
Cheong Tat Lou ◽  
Fan Yang ◽  
Kin Ian SiTou ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Viral Etiology ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

scholarly journals Effect of Zinc Salts on Respiratory Syncytial Virus Replication

2004 ◽  
Vol 48 (3) ◽  
pp. 783-790 ◽  
Author(s):  
Rahaman O. Suara ◽  
James E. Crowe
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Zinc Acetate ◽  
Lower Respiratory Tract ◽  
Divalent Cations ◽  
Cell Monolayer ◽  
Inhibitory Effect ◽  
Plaque Formation ◽  
Zinc Salts ◽  
Syncytial Virus

ABSTRACT Zinc supplementation decreases the morbidity of lower respiratory tract infection in pediatric patients in the developing world. We sought to determine if zinc mediates a specific inhibitory effect against the major cause of pediatric lower respiratory tract disease, respiratory syncytial virus (RSV). We determined the in vitro inhibitory effect of three zinc salts (zinc acetate, lactate, and sulfate) on the replication of RSV at various concentrations of 10 and 1 mM and 100 and 10 μM. The degree of inhibition of RSV replication was examined in the presence of zinc during preincubation, adsorption, or penetration and was compared with that caused by salts of other divalent cations. Complete inhibition of RSV plaque formation was observed at 1 and 10 mM, representing reductions that were ≥106-fold. At the lowest concentration tested, 10 μM, we observed ≥1,000-fold reductions in RSV yield when zinc was present during preincubation, adsorption, penetration, or egress of virus. The therapeutic indices, determined as ratios of 50% toxicity concentration to 50% inhibitory concentration, were 100, 150, and 120 for zinc acetate, zinc lactate, and zinc sulfate, respectively. The inhibitory effect of zinc salts on RSV was concentration dependent and was not observed with other salts containing divalent cations such as calcium, magnesium, and manganese. RSV plaque formation was prevented by pretreatment of HEp-2 cell monolayer cultures with zinc or by addition of zinc to methylcellulose overlay media after infection. The results of this study suggest that zinc mediates antiviral activity on RSV by altering the ability of the cell to support RSV replication.

Day-Care Center Attendance and Hospitalization for Lower Respiratory Tract Illness

PEDIATRICS ◽  
1988 ◽  
Vol 82 (3) ◽  
pp. 300-308
Author(s):  
Larry J. Anderson ◽  
Robert A. Parker ◽  
Raymond A. Strikas ◽  
Jeffrey A. Farrar ◽  
Eugene J. Gangarosa ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Day Care ◽  
Lower Respiratory Tract ◽  
Care Center ◽  
Demographic Data ◽  
Care Home ◽  
Univariate Analysis ◽  
Day Care Center ◽  
Respiratory Tract Illness ◽  
Syncytial Virus

To identify risk factors associated with hospitalization for acute lower respiratory tract illness, 102 children <2 years of age admitted to four Atlanta metropolitan area hospitals between December 1984 and June 1985 with the diagnosis of lower respiratory tract illness were studied. The most common causative agent associated with illness was respiratory syncytial virus, followed by other respiratory viruses, Haemophilus influenzae, and Streptococcus pneumoniae. The 102 case-patients were compared with 199 age- and sex-matched controls. A parent or guardian for each patient and control was interviewed by telephone regarding demographic data, care outside the home, breast-feeding, previous medical history, allergies, and smoking and illness in household members. Five factors were associated with lower respiratory tract illness in both a univariate analysis and a multiple logistic regression model (P < .05). These factors were the number of people sleeping in the same room with the child, a lack of immunization the month before the patient was hospitalized, prematurity, a history of allergy, and regular attendance in a day-care center (more than six children in attendance). Care received outside of the home in a day-care home (less than or equal to six children in attendance) was not associated with lower respiratory tract illness. The suggestion made by our study and other studies was that for children <2 years of age, care outside of the home is an important risk factor for acquiring lower respiratory tract illness, as well as other infectious diseases, and that this risk can be reduced by using a day-care home instead of a day-care center.

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