Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial

Alansari, Khalid; Toaimah, Fatihi Hassan Soliman; Almatar, Daher Helmi; Tatawy, Lamiaa Awny El; Davidson, Bruce L.; Qusad, Mohammad Ibrahim Mohammad

doi:10.1542/peds.2018-2308

Cited by 47 publications

(24 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40,41 In contrast, therapeutic administration of either palivizumab or motavizumab to RSVinfected infants after hospitalization did not alter disease severity and the duration of hospitalization compared with placebotreated RSV-infected infants. 42,43 Thus, only pre-existing RSVspecific neutralizing antibodies are sufficient to reduce RSVassociated disease in humans, similar to our results reported here evaluating RSV-specific memory CD8 T cell-mediated disease in mice. Given the demonstrated ability for prophylactic administration of neutralizing antibodies to prevent RSV-associated disease in humans, it is likely that they will also be capable of mitigating potentially pathological responses mediated by human memory CD8 T cells.…”

Section: Discussionsupporting

confidence: 86%

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

2020

View full text Add to dashboard Cite

Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-γ. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-γ production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-γ levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines.Mucosal Immunology (2020) 13:507-517; https://doi.

show abstract

Section: Discussionsupporting

confidence: 86%

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

2020

View full text Add to dashboard Cite

show abstract

“…Palivizumab an anti-RSV antibody that binds both pre-and post-fusion forms of the RSV F protein is highly effective as prophylaxis against RSV in human infants [13]but is ineffective as antiviral treatment once infection has occurred. [14] Experiments in a cotton rat model of RSV bronchiolitis demonstrated that a combination of anti-RSV antibodies and immunomodulation with NSAIDs or steroids did improve clinical outcomes following infection in a way that monotherapy did not. [9,15] RSV fusion protein inhibitors (FPI) have shown somewhat better results in animal models.…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial of a combination of antiviral and nonsteroidal anti-inflammatory treatment in a bovine model of respiratory syncytial virus infection

et al. 2020

View full text Add to dashboard Cite

Introduction Bovine respiratory syncytial virus (RSV) is a valid model for human RSV and an important bovine pathogen. Very early administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have separately been shown to decrease the severity of bovine RSV. Our aims were to determine how long after RSV inoculation ibuprofen and GS-561937 can be administered with clinical benefit and whether using both was better than monotherapy. Materials and methods We conducted a blinded randomized placebo controlled trial of ibuprofen, GS-561937 (FPI), or combinations of the two initiated at 3 or 5 days after artificial infection with bovine RSV in 36 five to six-week-old Holstein calves (Bos taurus). We measured clinical scores, respiratory rate, and viral shedding daily for 10 days following inoculation. We estimated the average effect for each drug and compared treatment arms using mixed effects models. Results We found a significant decrease in clinical scores only in the combined treatment arms. This benefit was greater when treatment was initiated at 3 days rather than 5 days post infection with decreased clinical scores and lower respiratory rates at both time points. Ibuprofen alone started on day 3 increased, and FPI with ibuprofen started on day 3 decreased, viral shedding. Conclusion Dual therapy with Ibuprofen and FPI, on average, decrease clinical severity of illness in a bovine model of RSV when started at 3 and 5 days after infection.

show abstract

“…Although effective in prevention, palivizumab has no therapeutic effect in acute RSV infection. 96 Fusion inhibitors have gained the most attention with presatovir the most recent. Presatovir has undergone five phase II trials but has limited impact on viral load and had no effect on clinical features of RSV disease; clinical trials have been halted due to safety concerns.…”

Section: Antiviral Therapymentioning

confidence: 99%

Respiratory syncytial virus (RSV): a scourge from infancy to old age

Coultas¹,

Smyth²,

Openshaw³

2019

Thorax

122

110

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.

show abstract

Monoclonal Antibody Treatment of RSV Bronchiolitis in Young Infants: A Randomized Trial

Cited by 47 publications

References 30 publications

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

A randomized controlled trial of a combination of antiviral and nonsteroidal anti-inflammatory treatment in a bovine model of respiratory syncytial virus infection

Respiratory syncytial virus (RSV): a scourge from infancy to old age

Contact Info

Product

Resources

About