Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus

Portnoy, Jay M.; Hicks, Ralph A.; Pacheco, Freddy; Olson, Lloyd C.

doi:10.1128/aac.32.4.589

Cited by 16 publications

(9 citation statements)

References 14 publications

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“…Second, in our model, IFN-␣ was instilled prior to RSV infection, with the hope of preventing Th2-biased responses during reinfection, whereas in the human studies, IFN-␣ was administered as a therapy after RSV infection. One very important result of this human study is that it demonstrated that the use of IFN-␣ in infants is safe (34). In fact, RSV-infected infants ranging from 2 to 8 months old received daily maximal doses of 70,000 U of IFN-␣ per kg of body weight with no toxicity being observed.…”

Section: Discussionmentioning

confidence: 83%

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Cormier

Shrestha

Saravia

et al. 2014

J Virol

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Respiratory syncytial virus (RSV) infection is the number one cause of bronchiolitis in infants IMPORTANCE Respiratory syncytial virus (RSV) is the most significant cause of lower respiratory tract infection in infancy worldwide.Despite the dire need, we have failed to produce efficacious RSV vaccines or therapeutics. Part of the reason for this failure is our lack of understanding of how RSV interacts with the infant immune system to suppress the development of protective immunity. In the study described in the present paper, we used a neonatal mouse model, which more closely mimics human infants, to study the role of the innate immune system, particularly type I interferons (IFNs) and plasmacytoid dendritic cells (pDCs), in the pathogenesis of RSV infection. RSV infection in neonates induced limited type I IFN and pDC responses. IFN-␣ treatment or adoptive transfer of adult pDCs capable of producing IFN-␣ prior to neonatal RSV infection decreased Th2-biased immunopathogenesis during reinfection. These data suggest that IFN-␣ is a promising target for future RSV vaccine design.

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Section: Discussionmentioning

confidence: 83%

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Cormier

Shrestha

Saravia

et al. 2014

J Virol

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“…All 52 infants recovered from their respiratory syncytial virus infection. The duration of hospital stay ranged from four to 12 days with a mean of [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] (173) days. The duration of hospital stay was not further compared in the two groups as uniform discharge criteria were not applied during the study period.…”

Section: Resultsmentioning

confidence: 99%

Treatment of respiratory syncytial virus infection with recombinant interferon alfa-2a.

Sung

Yin

Oppenheimer

et al. 1993

Archives of Disease in Childhood

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however, had a significantly higher overall score for severity of illness at the start of treatment. More rapid drop of the clinical score was observed in the INF-a-2a group after treatment in the first three days and the two groups had similar clinical severity by day 3. There was no significant difference of the duration ofviral shedding in the two groups. In conclusion, the overall clinical improvement was greater in the treatment group over the first three days, but the duration of viral shedding was not altered.

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“…A broad-spectrum drug with activity against several major respiratory viruses could overcome many of these problems. Such a role had been envisaged for interferon [Monto et al, 1986;Portnoy et al, 1988], but results from clinical trials on the prevention of respiratory viral disease in the 1980s were disappointing [Tannock et al, 1988;Wiselka et al, 1991]. , and 10 (Â) mg/ml arbidol.…”

Section: Discussionmentioning

confidence: 98%

Antiviral activity of arbidol, a broad‐spectrum drug for use against respiratory viruses, varies according to test conditions

Brooks

Burtseva

Ellery

et al. 2011

Journal of Medical Virology

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The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8 µg/ml (0.41-22 nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6 µg/ml); greater inhibition occurred when end-points were expressed as TCID(50) s. For respiratory syncytial virus (RSV), a reduction in plaque size but not number was observed. However, when the drug was added to infected cultures (≥5 µg/ml), a 3-log reduction in titer occurred. Arbidol did not inhibit directly influenza A/Aichi/2/68 hemagglutinin (HA) or neuraminidase (NA) activity, but inhibition of fusion between the viral envelope and chicken red blood cells occurred when added at 0.1 µg/ml prior to infection. Arbidol induced changes to viral mRNA synthesis of the PB2, PA, NP, NA, and NS genes in MDCK cultures infected with influenza A/PR/8/34. There was no indirect evidence of enhancement of interferon-α by arbidol following infection with A/Aichi/2/68. Arbidol neither reduced lung viral titers nor caused a significant reduction of lung consolidation in BALB/c mice after administration by the oral and intraperitoneal (i.p.) routes and intranasal challenge with influenza A/Aichi/2/68. A small reduction in lung consolidation, but not viral titer, occurred after i.p. administration and subsequent challenge with RSV. The results indicate the potential of arbidol as a broad-spectrum respiratory antiviral drug.

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Pilot study of recombinant interferon alpha-2a for treatment of infants with bronchiolitis induced by respiratory syncytial virus

Cited by 16 publications

References 14 publications

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Limited Type I Interferons and Plasmacytoid Dendritic Cells during Neonatal Respiratory Syncytial Virus Infection Permit Immunopathogenesis upon Reinfection

Treatment of respiratory syncytial virus infection with recombinant interferon alfa-2a.

Antiviral activity of arbidol, a broad‐spectrum drug for use against respiratory viruses, varies according to test conditions

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