Respiratory syncytial virus therapy and prophylaxis: have we finally turned the corner?

Hegele, Richard G.

doi:10.1183/09031936.00012011

Cited by 5 publications

(5 citation statements)

References 12 publications

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“…28 Despite the inconsistent clinical data to human monoclonal antibodies, the high costs of these biologics can also be a formidable problem to the therapy of these infections. 29…”

Section: Viral Attachment Inhibitorymentioning

confidence: 99%

Antivirals for Respiratory Viral Infections: Problems and Prospects

Liu

Zhou

et al. 2016

Semin Respir Crit Care Med

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In the past two decades, several newly emerging and reemerging viral respiratory pathogens including several influenza viruses (avian influenza and pandemic influenza), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV), have continued to challenge medical and public health systems. Thereafter, the development of cost-effective, broad-spectrum antiviral agents is the urgent mission of both virologists and pharmacologists. Current antiviral developments have focused targets on viral entry, replication, release, and intercellular pathways essential for viral life cycle. Here, we review the current literature on challenges and prospects in the development of these antivirals.

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“…28 Despite the inconsistent clinical data to human monoclonal antibodies, the high costs of these biologics can also be a formidable problem to the therapy of these infections. 29…”

Section: Viral Attachment Inhibitorymentioning

confidence: 99%

Antivirals for Respiratory Viral Infections: Problems and Prospects

Liu

Zhou

et al. 2016

Semin Respir Crit Care Med

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“…Palivizumab and long-acting nirsevimab are monoclonal antibodies that are administered prophylactically to high-risk children to prevent severe respiratory disease. In addition to supportive care, aerosolized or oral ribavirin, a nucleoside analog, is used to treat severe lower respiratory tract infections in hospitalized pediatric patients (11)(12)(13)(14). Candidate RSV therapeutics in development include agents that target virus entry (RSV F protein inhibitors) or virus replication (polymerase inhibitors) (15).…”

Section: Introductionmentioning

confidence: 99%

RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia

De,

Pickles,

Yao

et al. 2024

Front. Virol.

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Respiratory syncytial virus (RSV) is a substantial cause of severe lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. There is a vital need for effective therapeutics to prevent and/or treat severe RSV infection in these high-risk individuals. The development and pre-clinical testing of candidate RSV therapeutics could be accelerated by their evaluation in animal models that recapitulate bronchiolitis and bronchopneumonia, both hallmark features of severe RSV infection in humans. Previously, we demonstrated that implanted human lung tissue in humanized lung-only mice (LoM) can be infected with RSV, resulting in sustained virus replication. Here we analyzed RSV-associated human lung pathology in the human lung implants of RSV-infected LoM. RSV-infected epithelial cells lining the airway and the alveolar regions of human lung implants result in hallmark histological features of RSV bronchiolitis and bronchopneumonia, including distal airway and alveolar lumens clogged with (1) sloughed and necrotic RSV-infected epithelial cells, (2) neutrophil-containing inflammatory infiltrates, and (3) MUC5B-dominated mucus secretions. We also show that treatment of LoM with a small molecule antiviral (ribavirin) or a neutralizing antibody (palivizumab) significantly suppressed and/or prevented RSV infection in vivo. Our data together show that RSV infection of human lung implants in vivo exhibits appropriate cellular tropism and results in the hallmark pathological characteristics of severe bronchiolitis and bronchopneumonia in humans. They also offer proof-of-principle of the utility of this model to evaluate novel approaches for the prevention/treatment of RSV infection.

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“…The single-dose long-acting monoclonal antibody niresivamib was also recently approved by the European Union for RSV prevention in infants. Additional RSV antivirals have been developed, but despite promising preclinical efficacy, they failed to achieve efficacy and safety in larger clinical trials ( 9 , 10 ). There is a major need for an RSV vaccine, especially for infants and young children.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, 2 therapeutics are approved to treat RSV infection: a monoclonal antibody, palivizumab (Synagis), and the antiviral nucleoside analog, ribavirin. Palivizumab is used prophylactically for preventing severe RSV infections in high-risk children, and ribavirin is used to limit the severity of established RSV infections (8)(9)(10). The single-dose long-acting monoclonal antibody niresivamib was also recently approved by the European Union for RSV prevention in infants.…”

Section: Introductionmentioning

confidence: 99%

Human T cells efficiently control RSV infection

De¹,

Pickles²,

Yao³

et al. 2023

JCI Insight

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Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in infants, immunocompromised individuals, and older individuals. There is an urgent need for effective antivirals and vaccines for high-risk individuals. We used 2 complementary in vivo models to analyze RSV-associated human lung pathology and human immune correlates of protection. RSV infection resulted in widespread human lung epithelial damage, a proinflammatory innate immune response, and elicited a natural adaptive human immune response that conferred protective immunity. We demonstrated a key role for human T cells in controlling RSV infection. Specifically, primed human CD8 + T cells or CD4 + T cells effectively and independently control RSV replication in human lung tissue in the absence of an RSV-specific antibody response. These preclinical data support the development of RSV vaccines, which also elicit effective T cell responses to improve RSV vaccine efficacy.

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Respiratory syncytial virus therapy and prophylaxis: have we finally turned the corner?

Cited by 5 publications

References 12 publications

Antivirals for Respiratory Viral Infections: Problems and Prospects

Antivirals for Respiratory Viral Infections: Problems and Prospects

RSV infection of humanized lung-only mice induces pathological changes resembling severe bronchiolitis and bronchopneumonia

Human T cells efficiently control RSV infection

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