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Pharmaceutical Research May 2023With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents... (Review)
Review
With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.
Topics: Humans; Respiratory Syncytial Virus Infections; SARS-CoV-2; COVID-19; Antiviral Agents; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Vaccines
PubMed: 37186073
DOI: 10.1007/s11095-023-03520-1 -
Frontiers in Cellular and Infection... 2023Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised...
Acute respiratory infections are a group of diseases caused by viruses, bacteria, and parasites that mainly affect children until the age of 5 and immunocompromised senior adults. In Mexico, these infections are the main cause of morbidity in children, with more than 26 million cases of respiratory infections reported by the Secretariat of Health, in 2019. The human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV), and the human parainfluenza-2 (hPIV-2) are responsible for many respiratory infections. Currently, palivizumab, a monoclonal antibody against the fusion protein F, is the treatment of choice against hRSV infections. This protein is being studied for the design of antiviral peptides that act by inhibiting the fusion of the virus and the host cell. Therefore, we examined the antiviral activity of the HRA2pl peptide, which competes the heptad repeat A domain of the F protein of hMPV. The recombinant peptide was obtained using a viral transient expression system. The effect of the fusion peptide was evaluated with an entry assay. Moreover, the effectiveness of HRA2pl was examined in viral isolates from clinical samples obtained from patients with infections caused by hRSV, hMPV, or hPIV-2, by evaluating the viral titer and the syncytium size. The HRA2pl peptide affected the viruses' capacity of entry, resulting in a 4-log decrease in the viral titer compared to the untreated viral strains. Additionally, a 50% reduction in the size of the syncytium was found. These results demonstrate the antiviral potential of HRA2pl in clinical samples, paving the way toward clinical trials.
Topics: Child; Adult; Humans; Antiviral Agents; Paramyxoviridae Infections; Pneumovirus; Metapneumovirus; Peptides; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 37153148
DOI: 10.3389/fcimb.2023.1125135 -
Cureus Mar 2023With an increasing global incidence in children younger than the age of five, respiratory syncytial virus (RSV) is one of the most common viral respiratory infections... (Review)
Review
With an increasing global incidence in children younger than the age of five, respiratory syncytial virus (RSV) is one of the most common viral respiratory infections worldwide. Despite the increasing number of cases among infants and young children, RSV can infect any age group; however, some individuals are more high risk than others. Premature infants, young children, elderly, and immunocompromised individuals are the most likely to suffer a more severe presentation of RSV in comparison to healthy adults. RSV is transmitted through respiratory droplets via direct contact with an infected individual or with contaminated surfaces. The viral genome of RSV consists of 11 proteins. Out of these 11, two proteins allow for the attachment of the virus to the respiratory epithelial cells and fusion with host cells. Upon fusion, the viral material transfers to the host cell, where viral replication occurs. It is important to acknowledge that an individual is considered infectious and can transmit the virus even before the symptomatic presentation of RSV begins. As long as the individual is shedding the virus, he or she is considered infectious. The length of viral shedding also differs depending on the severity of the infection, who is infected, and the underlying immune status of an individual. Currently, there is no definitive treatment for RSV; however, supportive therapy is considered the mainstay treatment. Some pharmaceutical treatments such as ribavirin have been FDA-approved; however, the administration is typically limited to children and infants. Palivizumab is also administered as an immune prophylaxis; however, both therapies are constantly at the end of a cost-effective debate due to their extensively expensive nature and questionable adverse effect profiles. Supportive therapy includes hydration, supplemental oxygen, and mechanical ventilation in hospitalized cases; however, most RSV cases can be treated as outpatient cases. Prevention techniques such as hand washing and maintaining social distancing are imperative to minimize the transmission of the virus as much as remotely possible.
PubMed: 37082497
DOI: 10.7759/cureus.36342 -
Journal of Medical Economics 2023To assess the cost-utility of palivizumab no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35...
Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants.
BACKGROUND AND OBJECTIVE
To assess the cost-utility of palivizumab no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32-35 weeks' gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST).
METHODS
A decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included.
RESULTS
Cost quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231).
CONCLUSIONS
Palivizumab was highly cost-effective ( no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 7, respectively), captures more potential RSVHs (85% 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.
Topics: Infant; Infant, Newborn; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Antiviral Agents; Infant, Premature; Canada; Risk Factors; Hospitalization
PubMed: 37067826
DOI: 10.1080/13696998.2023.2202600 -
Infection and Drug Resistance 2023Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing... (Review)
Review
Since the discovery of the human respiratory syncytial virus (hRSV), multiple research efforts have been conducted to develop vaccines and treatments capable of reducing the risk of severe disease, hospitalization, long-term sequelae, and death from this pathogen in susceptible populations. In this sense, therapies specifically directed against hRSV are mainly based on monoclonal and polyclonal antibodies such as intravenous IgG (IVIG)-RSV and the monoclonal antibody palivizumab. However, these therapies are associated with significant limitations, including the need for the recruitment of a high number of convalescent volunteers who donate blood to procure IVIG-RSV and the costs associated with the need for repeated administrations of palivizumab. These limitations render this product not cost-effective for populations other than high-risk patients. These problems have underscored that it is still necessary to identify new safe and effective therapies for human use. However, these new therapies must benefit from a comparatively cheap production cost and the opportunity to be available to the high-risk population and anyone who requires treatment. Here, we review the different antibodies used to prevent the pathology caused by hRSV infection, highlighting therapies currently approved for human use and their clinical value. Also, the new, most promising candidates based on preclinical studies and clinical trial results are revised.
PubMed: 37063935
DOI: 10.2147/IDR.S379660 -
BMC Medicine Mar 2023Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a...
BACKGROUND
Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a shortacting monoclonal antibody (mAb), palivizumab (PVZ) that is expensive and intensive to administer, making it poorly suited for low-resource settings. Currently, new longer acting RSV mAbs and maternal vaccines are emerging from late-stage clinical development with promising clinical effectiveness. However, evidence of economic value and affordability must also be considered if these interventions are to be globally accessible. This systematic review's objective was to summarise existing evidence on the cost-of-illness (COI) and cost-effectiveness of RSV prevention interventions in LMICs.
METHODS
We conducted a systematic literature review using the Embase, MEDLINE, and Global Index Medicus databases for publications between Jan 2000 and Jan 2022. Two categories of studies in LMICs were targeted: cost-of-illness (COI) of RSV episodes and cost-effectiveness analyses (CEA) of RSV preventive interventions including maternal vaccines and long-acting mAbs. Of the 491 articles reviewed, 19 met the inclusion criteria.
RESULTS
COI estimates varied widely: for severe RSV, the cost per episode ranged from $92 to $4114. CEA results also varied-e.g. evaluations of long-acting mAbs found ICERs from $462/DALY averted to $2971/DALY averted. Study assumptions of input parameters varied substantially and their results often had wide confidence intervals.
CONCLUSIONS
RSV represents a substantial disease burden; however, evidence of economic burden is limited. Knowledge gaps remain regarding the economic value of new technologies specifically in LMICs. Further research is needed to understand the economic burden of childhood RSV in LMICs and reduce uncertainty about the relative value of anticipated RSV prevention interventions. Most CEA studies evaluated palivizumab with fewer analyses of interventions in development that may be more accessible for LMICs.
Topics: Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Antibodies, Monoclonal; Cost-Effectiveness Analysis
PubMed: 37004038
DOI: 10.1186/s12916-023-02792-z -
Therapeutic Advances in Infectious... 2023Respiratory syncytial virus (RSV) is a poor inducer of antiviral interferon (IFN) responses which result in incomplete immunity and RSV disease. Several RSV proteins...
BACKGROUND
Respiratory syncytial virus (RSV) is a poor inducer of antiviral interferon (IFN) responses which result in incomplete immunity and RSV disease. Several RSV proteins alter antiviral responses, including the non-structural proteins (NS1, NS2) and the major viral surface proteins, that is, fusion (F) and attachment (G) proteins. The G protein modifies the host immune response to infection linked in part through a CX3 C chemokine motif. Anti-G protein monoclonal antibodies (mAbs), that is, clones 3D3 and 2D10 that target the G protein CX3C chemokine motif can neutralize RSV and inhibit G protein-CX3CR1 mediated chemotaxis.
OBJECTIVES
Determine how monoclonal antibodies against the RSV F and G proteins modify the type I and III IFN responses to RSV infection.
DESIGN
As the G protein CX3 C motif is implicated in IFN antagonism, we evaluated two mAbs that block G protein CX3C-CX3CR1 interaction and compared responses to isotype mAb control using a functional cellular assay and mouse model.
METHODS
Mouse lung epithelial cells (MLE-15 cells) and BALB/c mice were infected with RSV Line19 F following prophylactic mAb treatment. Cell supernatant or bronchoalveolar lavage fluid (BALF) were assayed for types I and III IFNs. Cells were interrogated for changes in IFN-related gene expression.
RESULTS
Treatment with an anti-G protein mAb (3D3) resulted in improved IFN responses compared with isotype control following infection with RSV, partially independently of neutralization, and this was linked to upregulated SOCS1 expression.
CONCLUSIONS
These findings show that anti-G protein antibodies improve the protective early antiviral response, which has important implications for vaccine and therapeutic design.
PLAIN LANGUAGE SUMMARY
RSV is a leading cause of respiratory disease in infants and the elderly. The only Food and Drug Administration-approved prophylactic treatment is limited to an anti-F protein monoclonal antibody (mAb), that is, palivizumab which has modest efficacy against RSV disease. Accumulating evidence suggests that targeting the RSV attachment (G) protein may provide improved protection from RSV disease. It is known that the G protein is an IFN antagonist, and IFN has been shown to be protective against RSV disease. In this study, we compared IFN responses in mouse lung epithelial (MLE-15) cells and in mice infected with RSV Line19 F treated with anti-G protein or anti-F protein mAbs. The levels of type I and III IFNs were determined. Anti-G protein mAbs improved the levels of IFNs compared with isotype-treated controls. These findings support the concept that anti-G protein mAbs mediate improved IFN responses against RSV disease, which may enable improved treatment of RSV infections.
PubMed: 36938145
DOI: 10.1177/20499361231161157 -
Revista Paulista de Pediatria : Orgao... 2023Due to the high cost and short term of passive immunization against the respiratory syncytial virus, the main virus causing acute viral bronchiolitis, predicting...
Temporal-spatial analysis of hospitalizations for bronchiolitis in Brazil: prediction of epidemic regions and periods for immunization against the Respiratory Syncytial Virus.
OBJECTIVE
Due to the high cost and short term of passive immunization against the respiratory syncytial virus, the main virus causing acute viral bronchiolitis, predicting epidemic regions and epidemic months is extremely important. The objective of this study is to identify both the month when the seasonal peak begins and Brazilian regions and states with the highest incidence of monthly hospitalizations due acute viral bronchiolitis.
METHODS
Based on data obtained from DATASUS, monthly hospitalization rates due acute viral bronchiolitis were calculated for every 10,000 live births to children under 12 months of age in all Brazilian states and the Federal District between 2000 and 2019. Seasonal autoregressive integrated moving average models were estimated to forecast monthly hospitalization rates in 2020.
RESULTS
A higher incidence of hospitalizations was found for male children, especially under six months of age. As for Brazilian regions, between 2000 and 2019, the South region registered the highest incidence of hospitalizations, followed by the Southeast, Midwest, North and Northeast regions, in this order. Considering the seasonal peak, the period between March and July 2020 comprised the highest expected hospitalization rates.
CONCLUSIONS
Palivizumab is suggested to be started between February/March and June/July for most Brazilian states, with the exception of Rio Grande do Sul, which, in addition to presenting the highest rates of hospitalizations for acute viral bronchiolitis per 10,000 live births, has the longest seasonal peak between May and September.
Topics: Child; Male; Humans; Infant; Respiratory Syncytial Viruses; Brazil; Respiratory Syncytial Virus Infections; Bronchiolitis, Viral; Bronchiolitis; Hospitalization; Pneumonia; Immunization; Spatial Analysis
PubMed: 36921162
DOI: 10.1590/1984-0462/2023/41/2021304 -
Children (Basel, Switzerland) Jan 2023Among prematurely born infants and newborns with chronic conditions, a respiratory syncytial virus (RSV) infection may cause (re-)admission and later respiratory...
Among prematurely born infants and newborns with chronic conditions, a respiratory syncytial virus (RSV) infection may cause (re-)admission and later respiratory complications. Therapeutic protection is possible with monthly injections of a specific monoclonal antibody, palivizumab, during RSV season. Standard care is giving up to five injections in clinic-based settings. Immunization at home could be an alternative to standard care for vulnerable infants to reduce the number of revisits and associated risk of RSV infection. The aim of this randomized pilot trial was to evaluate safety aspects and explore parents' preferences of home versus hospital immunization with palivizumab during one RSV season. Immediate adverse events (AEs) were observed and registered by a pediatric specialist nurse. Late-onset AEs were reported by parents. Parents' perceptions were collected through a questionnaire and analyzed using content analysis. The study population consisted of 43 infants in 38 families. No immediate AEs occurred. Three late-onset AEs were reported in two infants in the intervention group. Three categories emerged in the content analysis: (1) protect and watch over the infant, (2) optimal health and well-being for the whole family, and (3) avoid suffering for the infant. The study results show that home immunization with palivizumab is feasible if safety aspects are considered and that parental involvement in the choice of place for immunization after a neonatal intensive care experience can be important.
PubMed: 36832327
DOI: 10.3390/children10020198 -
Journal of Mother and Child Mar 2022The aim of this research is to determine the specific characteristics of the immunized children during a 15-year period and the readmissions to hospital due to potential...
AIM
The aim of this research is to determine the specific characteristics of the immunized children during a 15-year period and the readmissions to hospital due to potential infections of the respiratory tract.
MATERIAL AND METHODS
This retrospective cohort study was conducted in the period from October 2008 to March 2022. The test group consists of 222 infants who met the strict criteria for immunization.
RESULTS
The study observed 222 infants who were immunized with palivizumab during the 14-year period. 124 (55.9%) infants were preterm (< 32 weeks) and 69 (31.1%) were infants with congenital heart defects, whereas 29 (13.1%) exhibited other individual risk factors. 38 (17.1%) were re-admitted to the pulmonary ward. Upon re-admission, a quick test to diagnose for RSV infections was conducted and only one infant tested positive.
RESULTS
The conclusion of our 14-year study is that palivizumab prophylaxis has truly proven itself effective for infants at risk in our region during the research time period. Over the years, the immunization season has not changed and the number of doses hasremained the same, as have the indications for immunization. What has changed, however, is an increase in the number of immunized infants without a significant increase in the number of re-admissions to hospital on account of respiratory disorders.
Topics: Infant, Newborn; Humans; Child; Palivizumab; Antiviral Agents; Retrospective Studies; Respiratory Syncytial Virus Infections; Immunization
PubMed: 36811495
DOI: 10.34763/jmotherandchild.20222601.d-22-00049