Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00097 (anti-RSV)
 466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine to prevent RSV infection, and the available therapeutic agents are of limited utility. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMOs, designed to target sequence that includes the 5'-terminal region and translation start-site region of RSV L mRNA, were tested for anti-RSV activity in cultures of two human-airway cell lines. Both PPMOs showed minimal cytotoxicity and one of them, (AUG-2), reduced viral titers by >2.0 log(10). Intranasal (i.n.) treatment of BALB/c mice with AUG-2 PPMO before the RSV inoculation produced a reduction in viral titer of 1.2 log(10) in lung tissue at day 5 postinfection (p.i.), and attenuated pulmonary inflammation at day 7 postinfection. These data show that the AUG-2 PPMO possesses potent anti-RSV activity and is worthy of further investigation as a candidate for potential therapeutic application.
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PMID:Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice. 1844 2

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infections. Protection against infection with RSV can be achieved by monthly administration of the humanized monoclonal antibody palivizumab. The present study analyzes if genetic delivery of a murine version of palivizumab by single administration would achieve high-level and sustained antibody expression to protect mice against pulmonary infection with RSV. A murine version of the palivizumab antibody was constructed by replacing the human sequences with sequences from the constant region of a murine IgG1 antibody, while preserving the complementarity-determining region. As a proof-of-principle to test the validity of the strategy, the coding sequence for the heavy and light chains were cloned into a replication-defective serotype 5 human adenovirus vector (AdalphaRSV). Antibody expression and specificity for RSV was confirmed by Western analysis. To determine if AdalphaRSV would mediate production of anti-RSV antibodies in vivo, 5x10(10) particle units of AdalphaRSV or a control vector without transgene (AdNull), were administered intravenously to BALB/c mice. RSV neutralizing antibodies were detected in the serum after 4 days in mice receiving AdalphaRSV but not in AdNull-infected or naive mice (p<0.05). The mice that had received AdalphaRSV had at least 5.4-fold lower RSV titers in the lung 4 days following intranasal challenge with RSV compared to the AdNull or naive group (p<0.01). To evaluate long-term protection, the antibody construct was expressed in a non-human primate serotype rh.10 adeno-associated virus vector (AAVrh.10alphaRSV). RSV neutralizing antibodies were detected in serum and bronchoalveolar lavage fluid for up to 21 wk following intrapleural administration of AAVrh.10alphaRSV, but not with a control AAV vector expressing an unrelated transgene (AAVrh.10alpha1AT). Following challenge with RSV at 7 or 21 wk, 14.3-fold and 10.6-fold lower RSV titers were observed after 4 days in the lungs of mice that had received AAVrh.10alphaRSV compared to AAVrh.10alpha1AT (p<0.05). Together these data demonstrate that a gene transfer strategy for delivery of an anti-RSV antibody can generate protective immunity in mice against RSV infection in the respiratory tract and may provide an alternative to the administration of the antibody itself.
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PMID:Genetic delivery of an anti-RSV antibody to protect against pulmonary infection with RSV. 1855 39

Respiratory syncytial virus (RSV) is a major cause of morbidity in infants, young children, and the elderly worldwide. Currently, there is no effective vaccine, and antiviral drugs to control infection are limited. RNA interference is a powerful tool amenable to development of antiviral drugs. Using small interfering RNA (siRNA) targeting the RSV P gene (siRNA-P), RSV replication can be silenced both in vitro and in a BALB/c model of RSV infection. In this study, we examine the effect of siRNA prophylaxis on the primary and memory immune response to RSV infection in mice. We show that mice prophylactically treated with siRNA-P to decrease but not eliminate RSV replication exhibit reduced pulmonary inflammation and lung pathogenesis and produce a robust anti-RSV memory response when subsequently challenged with RSV. The pulmonary T-cell memory response was characterized by high numbers of CD44(hi) CD62L(lo) CD4(+) and CD8(+) T cells, M2 peptide tetramer(+) CD8(+) T cells expressing gamma interferon, and an RSV-specific antibody response. The results support the hypothesis that siRNAs can be developed as effective antiviral drugs that can be used to reduce the viral load and parameters of pathogenesis without limiting the induction of the memory immune response.
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PMID:RNA interference inhibits respiratory syncytial virus replication and disease pathogenesis without inhibiting priming of the memory immune response. 1881 23

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections. In severely immunosuppressed patients RSV can cause significant morbidity and mortality. The only FDA-approved drug for RSV is aerosolized ribavirin. Given the high morbidity and mortality in high-risk populations and inconsistent results with aerosolized ribavirin, new strategies for prevention and treatment of RSV are being sought. Palivizumab is an RSV-specific monoclonal antibody. A randomized, double-blind, placebo-controlled multicenter study showed significant reduction in hospitalization rates among children at high risk of RSV infection who had been given prophylactic palivizumab; these findings led to palivizumab's approval by the FDA in June 1998. Palivizumab also has a role in prevention of severe respiratory tract infections in high-risk infants. In immunocompromised patients, palivizumab has an excellent safety profile and may be beneficial in the prevention and treatment of RSV infections; however, clinical trials are needed to determine its effectiveness. In this article, we review the role of palivizumab in prevention and treatment of RSV infections in immunocompetent and immunocompromised patients.
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PMID:Palivizumab: where to from here? 1906

Respiratory syncytial virus (RSV) has been demonstrated to cause substantial disease in elderly and immunocompromised subjects. The relationship of serum antibody to RSV infection and the risk of infection in elderly subjects is controversial, thus we evaluated the presence of neutralizing antibodies to RSV in healthy people of different age groups and the correlation with viral protection. Baseline blood samples from 197 subjects aged 20-80 years were analysed for the presence of anti-RSV antibodies either by indirect immunofluorescence and microneutralization test. The percentage of people who had neutralizing antibodies to RSV was significantly higher (P=0.001) in the youngest group (92.51%) compared to the frail group (36.21%). The RSV antibody level tends to wane in some older people; this factor could determine proneness to RSV re-infections in the elderly who are at a greater risk of developing severe respiratory disease.
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PMID:Humoral immunity to respiratory syncytial virus in young and elderly adults. 1936 92

Because the G protein of respiratory syncytial virus (RSV) has a CX3C chemokine motif that has been associated with the ability of RSV G protein to modulate the virus-induced host immune response, we examined whether therapeutic treatment with an anti-RSV G monoclonal antibody (mAb), 131-2G, that blocks the CX3C-associated activity of RSV G protein might decrease the pulmonary inflammation associated with infection in BALB/c mice. The results show that treatment with mAb 131-2G on day 3 after RSV infection reduces both inflammation and RSV titer in the lungs. Later administration of anti-RSV G mAb (day 5 after RSV infection) effectively reduced the viral titer but had a minimal effect on pulmonary inflammation. This study suggests that an anti-RSV G mAb might be an effective antiviral, either alone or in combination with anti-RSV F protein neutralizing antibodies, for decreasing the virus-induced host response to infection and improve treatment outcome.
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PMID:Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice. 1954 10

An economic analysis was performed in Spain to evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe RSV infection in premature infants with GA 32-35 and two or more risk factors (RF). The design was a decision tree model using data from the scientific literature and the FLIP I and FLIP II studies IRIS Study Group. The main effectiveness measure was quality-adjusted life years (QALY) gained from both the National Health System (NHS) and societal perspectives. Prophylaxis with palivizumab was found to produce an incremental cost-effectiveness ratio (ICER) of 13,849euro/QALY from the NHS perspective, and 4,605euro/QALY from the societal perspective. Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favourable scenarios, is lower than the threshold of 30,000euro/QALY considered socially acceptable in Europe.
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PMID:Health economics and RSV. 1965 92

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children less than 1 year of age and causes substantial morbidity. Although there is not currently a vaccine available to prevent RSV infection, prophylaxis with the humanized monoclonal antibody palivizumab has been shown to reduce the rate of RSV hospitalization in premature infants and those infants with chronic lung disease or congenital heart disease. Because palivizumab has not been shown to have a beneficial clinical effect on established RSV disease such as reducing the rate of mechanical ventilation and mortality in children afflicted with RSV, there has been considerable debate as to the cost-benefit ratio of administering palivizumab according to international guidelines. Palivizumab has demonstrated a favorable side-effect profile in clinical trials without the development of anti-palivizumab antibodies. Future studies are needed to determine whether palivizumab, or other more potent monoclonal antibodies which are currently undergoing clinical trials, will reduce the long-term sequelae of RSV infection such as the development of wheezing and asthma.
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PMID:Palivizumab: a review of its use in the protection of high risk infants against respiratory syncytial virus (RSV). 1970 46

Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.
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PMID:Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of respiratory syncytial virus G protein reduces pulmonary inflammation and virus replication in mice. 1986 90

This study was performed to evaluate the utilization and outcomes of palivizumab in high risk children born prematurely with chronic lung disease (CLD). A retrospective review of 128 patients was conducted from September 2004 to March 2009 at the Ajou University Hospital. All patients were diagnosed with CLD, were born at <or=35 weeks of gestation, were <2 yr old at the onset of respiratory syncytial virus (RSV) season, and had received medical therapy within six months prior to the RSV season. Fifty-three patients did not receive palivizumab prophylaxis and 75 patients received at least one dose of palivizumab. There were no statistically significant differences between the patients with and without palivizumab prophylaxis with regard to demographic characteristics and risk factors for RSV infection. There were no systemic adverse responses. Compliance with the course of prophylaxis was 92.2%. Hospitalization associated with RSV occurred in 12 cases (22.6%) in the group without prophylaxis and in three cases (4.0%) with prophylaxis. Palivizumab prophylaxis significantly reduced the frequency of RSV-related hospitalization in preterm children with CLD. This is the first retrospective review of palivizumab prophylaxis in Korea. Palivizumab is effective and well tolerated in high risk prematurely born children.
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PMID:Outcomes of palivizumab prophylaxis for respiratory syncytial virus infection in preterm children with bronchopulmonary dysplasia at a single hospital in Korea from 2005 to 2009. 2011 79


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