Table 1.
Schema for Toxicity Study Evaluating Systemic VSV-hIFNβ-NIS Administration in Normal Dogs Including a Study Schedule for Observation and Sample Collection to Monitor Clinical Toxicities, Virus Pharmacokinetics, Shedding, and Antiviral Immune Responses
| Time point (days) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Monitoring | <0 | 1 | 3 | 5 | 7 | 10 | 15 | 21 | 30 | 45 | |
| Clinical symptoms | Continual | ||||||||||
| Virus pharmacokinetics | • | ||||||||||
| Labwork: CHEM/CBC/COAG/urinalysis | • | • | • | • | • | • | • | • | • | • | |
| Shedding: Blood, urine, buccal swabs, feces | qRT-PCR | • | • | • | • | • | • | • | • | • | • |
| IVR | • | • | • | • | • | • | • | • | • | • | |
| Immune response: Anti-VSV antibodies IgG/IgM | PRN | • | • | • | • | • | • | • | • | • | • |
| ELISA | • | • | • | • | • | • | • | • | • | • | |
Dots in vertical direction indicate single IV dose of VSV-IFNβ-NIS; dots in horizontal direction indicate acute and chronic toxicity monitoring.
CBC, complete blood count; CHEM, blood chemistry; COAG, blood coagulation; ELISA, enzyme-linked immunosorbent assay; IVR, infectious virus recovery; PRN, plaque reduction neutralization; qRT-PCR, quantitative reverse transcription–polymerase chain reaction; VSV-hIFNβ-NIS, vesicular stomatitis virus expressing human interferon-beta and the sodium iodide symporter.