Comparing inluenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals

Bindiya Bagga, Christopher W. Woods, Timothy H. Veldman, Anthony Gilbert, Alex Mann, Ganesh Balaratnam, Robert Lambkin-Williams, John S. Oxford, Micah T. McClain, Tom Wilkinson, Brad P. Nicholson, Geoffrey S. Ginsburg, John Devincenzo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Antivirals reduce inluenza viral replication and illness measures, particularly if initiated early, within 48 h of symptom onset. Whether experimental antivirals that reduce respiratory syncytial virus (RSV) load would also reduce disease is unknown. This study compares viral and disease dynamics in humans experimentally infected with inluenza or RSV. Methods: Clinical strains of RSV-A and inluenza A were inoculated intranasally into 20 and 17 healthy volunteers, respectively, on day 0. Symptom scores and nasal washes were performed twice daily, and daily mucus weights were collected. Viral loads in nasal washes were quantiied by culture (plaque assay in HEp-2 cells for RSV and by end point dilution in Madin-Darby canine kidney cells for inluenza). Results: After inluenza inoculation, inluenza viral load and illness markers increased simultaneously until day 2. Within individual subjects, peak inluenza load occurred 0.4 days (95% CI -0.4, 1.3) before peak symptoms. Inluenza viral load and disease declined thereafter. After RSV inoculation, a longer incubation period occurred prior to viral detection and symptom onset. RSV load and disease increased together until day 5. Within individual subjects, peak RSV loads occurred 0.2 days (95% CI -0.7, 1.05) before peak symptoms, after which both illness measures and viral load declined together. Conclusions: Viral and disease dynamics in experimental human infections suggest that reducing RSV load, if timed similarly to clinically-effective inluenza antivirals, might be expected to have a similar or greater window of opportunity for reducing clinical RSV disease.

Original languageEnglish (US)
Pages (from-to)785-791
Number of pages7
JournalAntiviral Therapy
Volume18
Issue number6
DOIs
StatePublished - Dec 1 2013

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Respiratory Syncytial Viruses
Virus Diseases
Antiviral Agents
Viral Load
Nose
Madin Darby Canine Kidney Cells
Mucus
Healthy Volunteers
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Comparing inluenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals. / Bagga, Bindiya; Woods, Christopher W.; Veldman, Timothy H.; Gilbert, Anthony; Mann, Alex; Balaratnam, Ganesh; Lambkin-Williams, Robert; Oxford, John S.; McClain, Micah T.; Wilkinson, Tom; Nicholson, Brad P.; Ginsburg, Geoffrey S.; Devincenzo, John.

In: Antiviral Therapy, Vol. 18, No. 6, 01.12.2013, p. 785-791.

Research output: Contribution to journalArticle

Bagga, B, Woods, CW, Veldman, TH, Gilbert, A, Mann, A, Balaratnam, G, Lambkin-Williams, R, Oxford, JS, McClain, MT, Wilkinson, T, Nicholson, BP, Ginsburg, GS & Devincenzo, J 2013, 'Comparing inluenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals', Antiviral Therapy, vol. 18, no. 6, pp. 785-791. https://doi.org/10.3851/IMP2629
Bagga, Bindiya ; Woods, Christopher W. ; Veldman, Timothy H. ; Gilbert, Anthony ; Mann, Alex ; Balaratnam, Ganesh ; Lambkin-Williams, Robert ; Oxford, John S. ; McClain, Micah T. ; Wilkinson, Tom ; Nicholson, Brad P. ; Ginsburg, Geoffrey S. ; Devincenzo, John. / Comparing inluenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals. In: Antiviral Therapy. 2013 ; Vol. 18, No. 6. pp. 785-791.
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AU - Bagga, Bindiya

AU - Woods, Christopher W.

AU - Veldman, Timothy H.

AU - Gilbert, Anthony

AU - Mann, Alex

AU - Balaratnam, Ganesh

AU - Lambkin-Williams, Robert

AU - Oxford, John S.

AU - McClain, Micah T.

AU - Wilkinson, Tom

AU - Nicholson, Brad P.

AU - Ginsburg, Geoffrey S.

AU - Devincenzo, John

PY - 2013/12/1

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N2 - Background: Antivirals reduce inluenza viral replication and illness measures, particularly if initiated early, within 48 h of symptom onset. Whether experimental antivirals that reduce respiratory syncytial virus (RSV) load would also reduce disease is unknown. This study compares viral and disease dynamics in humans experimentally infected with inluenza or RSV. Methods: Clinical strains of RSV-A and inluenza A were inoculated intranasally into 20 and 17 healthy volunteers, respectively, on day 0. Symptom scores and nasal washes were performed twice daily, and daily mucus weights were collected. Viral loads in nasal washes were quantiied by culture (plaque assay in HEp-2 cells for RSV and by end point dilution in Madin-Darby canine kidney cells for inluenza). Results: After inluenza inoculation, inluenza viral load and illness markers increased simultaneously until day 2. Within individual subjects, peak inluenza load occurred 0.4 days (95% CI -0.4, 1.3) before peak symptoms. Inluenza viral load and disease declined thereafter. After RSV inoculation, a longer incubation period occurred prior to viral detection and symptom onset. RSV load and disease increased together until day 5. Within individual subjects, peak RSV loads occurred 0.2 days (95% CI -0.7, 1.05) before peak symptoms, after which both illness measures and viral load declined together. Conclusions: Viral and disease dynamics in experimental human infections suggest that reducing RSV load, if timed similarly to clinically-effective inluenza antivirals, might be expected to have a similar or greater window of opportunity for reducing clinical RSV disease.

AB - Background: Antivirals reduce inluenza viral replication and illness measures, particularly if initiated early, within 48 h of symptom onset. Whether experimental antivirals that reduce respiratory syncytial virus (RSV) load would also reduce disease is unknown. This study compares viral and disease dynamics in humans experimentally infected with inluenza or RSV. Methods: Clinical strains of RSV-A and inluenza A were inoculated intranasally into 20 and 17 healthy volunteers, respectively, on day 0. Symptom scores and nasal washes were performed twice daily, and daily mucus weights were collected. Viral loads in nasal washes were quantiied by culture (plaque assay in HEp-2 cells for RSV and by end point dilution in Madin-Darby canine kidney cells for inluenza). Results: After inluenza inoculation, inluenza viral load and illness markers increased simultaneously until day 2. Within individual subjects, peak inluenza load occurred 0.4 days (95% CI -0.4, 1.3) before peak symptoms. Inluenza viral load and disease declined thereafter. After RSV inoculation, a longer incubation period occurred prior to viral detection and symptom onset. RSV load and disease increased together until day 5. Within individual subjects, peak RSV loads occurred 0.2 days (95% CI -0.7, 1.05) before peak symptoms, after which both illness measures and viral load declined together. Conclusions: Viral and disease dynamics in experimental human infections suggest that reducing RSV load, if timed similarly to clinically-effective inluenza antivirals, might be expected to have a similar or greater window of opportunity for reducing clinical RSV disease.

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