A review of palivizumab and emerging therapies for respiratory syncytial virus

Shadman, Kristin A.; Wald, Ellen R.

doi:10.1517/14712598.2011.608062

Cited by 55 publications

(45 citation statements)

References 83 publications

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“…Estimates suggest that each year, RSV leads to 3.4 million hospitalizations and at least 66,000 deaths in children under five years of age (Falsey et al, 2005; Hall et al, 2009; Nair et al, 2010; Shay et al, 1999). Despite ongoing efforts, there are no vaccines against RSV and the only treatments available are passive immunoprophylaxis (Shadman and Wald, 2011) and nebulized ribavirin (Smith et al, 1991). Clearly, new treatment strategies are needed.…”

Section: Introductionmentioning

confidence: 99%

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Hoffmann

Schneider

Blomen

et al. 2017

Cell Host & Microbe

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SUMMARY Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxo-, Flavi-, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the trans-Golgi network that require calcium for their activity and are critical for virus glycoprotein maturation. Consistent with these findings, viral glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread, which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an attractive antiviral host target for a broad spectrum of established and emerging viral infections.

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Section: Introductionmentioning

confidence: 99%

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Hoffmann

Schneider

Blomen

et al. 2017

Cell Host & Microbe

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“…A virus of the Family Paramyxoviridae , genus Pneumovirus, RSV is an enveloped single-stranded RNA virus that replicates in human alveolar macrophages and bronchial epithelial cells in vivo. While most disease is mild to moderate in nature, some infants are at high risk for severe disease, including those with bronchopulmonary dysplasia, immunodeficiency, premature birth and congenital heart disease; monoclonal antibody prophylaxis is available for these individuals [Shadman & Wald, 2011]. Although not currently available, research and development is ongoing toward a safe and effective RSV vaccine [Rudraraju et al , 2013].…”

Section: Introductionmentioning

confidence: 99%

Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFN γ ) gene-deleted mice

et al. 2014

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Interferon gamma (IFNγ) has complex immunomodulatory and antiviral properties. While IFNγ is detected in the airways in response to infection with the pneumovirus pathogen, pneumonia virus of mice (PVM; Family Paramyxoviridae), its role in promoting disease has not been fully explored. Here, we evaluate PVM infection in IFNγ−/− mice. Although the IFNγ gene-deletion has no impact on weight loss, survival or virus kinetics, expression of IFNβ, IFNλ2/3 and IFN-stimulated 2'–5' oligoadenylate synthetases was significantly diminished compared to wild-type counterparts. Furthermore, PVM infection in IFNγ−/− mice promoted prominent inflammation, including eosinophil and neutrophil infiltration into the airways and lung parenchyma, observed several days after peak virus titer. Potential mechanisms include over-production of chemoattractant and eosinophil-active cytokines (CXCL1, CCL11, CCL3 and IL5) in PVM-infected IFNγ−/− mice; likewise, IFNγ actively antagonized IL5-dependent eosinophil survival ex vivo. Our results may have clinical implications for pneumovirus infection in individuals with IFNγ signaling defects.

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“…were shown to induce inadequate protection, being under-or overattenuated in a variety of animal models (37,39,88). However, it is clear that anti-RSV F protein antibody responses are effective at neutralizing RSV (8,89,90), and this is further supported by studies examining the efficacy of palivizumab, which is a humanized antibody specific to the F protein and which has been approved for prophylactic use in children with certain risk factors (21,22,91). The RSV F protein has been shown to be a TLR4 and CD14 agonist (61).…”

Section: Figmentioning

confidence: 99%

“…The F protein binds to glycosaminoglycans (GAGs) and putatively nucleolin on host cells (20) and like HA is a major viral glycoprotein where antibodies to F protein neutralize RSV (21). One such antibody directed against RSV F protein is palivizumab (Synagis), which is used to treat premature infants and those at high risk for development of severe RSV infection (22,23).…”

mentioning

confidence: 99%

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

Turner

Jones

Tompkins

et al. 2013

J Virol

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Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity.

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A review of palivizumab and emerging therapies for respiratory syncytial virus

Abstract: Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.

Cited by 55 publications

References 83 publications

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Sustained inflammation and differential expression of interferons type I and III in PVM-infected interferon-gamma (IFN γ ) gene-deleted mice

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

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