Viral Induced Disease in Mild Atopic Asthmatics: Dynamics of Pulmonary Function, Speed of Symptom Onset and Implications for Drug Intervention in HRV Inoculated Volunteers

Abstract

The immune response in asthmatics has been shown to be different to non-asthmatics, leading to differences in the response to infection between the populations. This trial was performed to gather evidence about the optimum dose, safety, and pathogenicity of a GMP manufactured HRV-16 strain in asthmatics. hVIVO recruited 20 mild atopic asthmatics with low serum neutralizing antibodies. Subjects had full health screens including physical examinations, pulmonary function, and skin prick tests. Subjects were brought to quarantine a day before inoculation and randomized to either a 10TCID50 dose of virus (n=13) or placebo (n=7). Throughout the controlled quarantine period, regular timed samples were taken and assessments performed for 8 days, before discharge. Asthmatic data were compared to data obtained from healthy subjects given the same dose of virus. Of the 13 asthmatics inoculated with virus, 11 (85%) were infected (confirmed by PCR), 4 of the infected (36%) exacerbated (ACQ score rise by 0.5), and had measurable reductions in PEF. Interestingly the infected asthmatics had a more rapid onset of both upper and lower respiratory symptoms, preceding healthy subjects. A GMP HRV-16 strain of virus has safely progressed through the 1st two stages of characterization in volunteers. Mild asthmatics exacerbated upon inoculation with a low dose of HRV, had reductions in lung function and a rapid onset of symptoms. Robust assessments and sampling within quarantines can aid in reducing noise and could allow for more precise and dynamic measurement of drug efficacy.