Use of qualitative integrative cycler PCR (qicPCR) to identify optimal therapeutic dosing time-points in a Respiratory Syncytial Virus Human Viral Challenge Model (hVCM).
Retroscreen (hVIVO) have developed an RSV human viral challenge model (hVCM) for testing the efficacy of novel antiviral therapies by monitoring changes in viral load and symptoms. The integrated cycler technology and Simplexa™ kits (Focus Diagnostics) currently provide fast, qualitative and sensitive diagnostic testing in hospitals and other healthcare facilities for patients with well-established respiratory illness. We have developed a novel use of qualitative integrated cycler PCR (qicPCR) technology to identify onset of RSV infection enabling an informed dosing clinical protocol in the RSV hVCM. We have validated qicPCR detection of RSV in spiked nasal wash aspirates and demonstrate that the qicPCR assay is 94% concordant with RSV plaque assay data in nasal wash samples from 53 RSV inoculated human volunteers in the hVCM. The use of qicPCR for informed dosing was successfully implemented in a recent clinical trial demonstrating efficacy of the RSV entry inhibitor GS-5806 in the hVCM (NCT01756482). Comparison of qicPCR positivity in relation to nasal wash viral load measured by both RT-qPCR and plaque assay shows that the therapeutic exposure was correctly initiated prior to onset and peak of RSV viral shedding and symptoms in the majority of volunteers.
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Geraldine
G
Kelly
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Carl
C
Laxton
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Mariam
M
Garelnabi
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Brian
B
Alton
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Fatima
F
Addan
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Andrew
A
Catchpole
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Elaine
E
Thomas
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Daryl
D
Borley
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Kieran
K
Dee
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Alison
A
Boyers
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Erica
E
Bringas
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Nicolas
N
Noulin
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX.
Rob
R
Lambkin-Williams
Retroscreen Virology Limited (hVIVO), Queen Mary BioEnterprises Innovation Centre, 42, New Road, Whitechapel, London E1 2AX. Electronic address: t.murray@retroscreen.com.
Edward J
EJ
Murray
D000998:Antiviral Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D006801:Humans; D009296:Nasal Cavity / Q000821:virology*; D016133:Polymerase Chain Reaction / Q000379:methods*; D018357:Respiratory Syncytial Virus Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification*; D019562:Viral Load / Q000379:methods*
D000998:Antiviral Agents
RSV challenge model (hVCM); RSV clinical trials; qicPCR