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Abstract
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children and is responsible for as many as 199,000 childhood deaths annually worldwide. To support the development of viral therapeutics and vaccines for RSV, a human adult experimental infection model has been established. In this report, we describe the provenance and sequence of RSV Memphis-37, the low-passage clinical isolate used for the model's reproducible, safe, experimental infections of healthy, adult volunteers. The predicted amino acid sequences for major proteins of Memphis-37 are compared to nine other RSV A and B amino acid sequences to examine sites of vaccine, therapeutic, and pathophysiologic interest. Human T- cell epitope sequences previously defined by in vitro studies were observed to be closely matched between Memphis-37 and the laboratory strain RSV A2. Memphis-37 sequences provide baseline data with which to assess: (i) virus heterogeneity that may be evident following virus infection/transmission, (ii) the efficacy of candidate RSV vaccines and therapeutics in the experimental infection model, and (iii) the potential emergence of escape mutants as a consequence of experimental drug treatments. Memphis-37 is a valuable tool for pre-clinical research, and to expedite the clinical development of vaccines, therapeutic immunomodulatory agents, and other antiviral drug strategies for the protection of vulnerable populations against RSV disease.
Highlights
Respiratory syncytial virus (RSV) is a paramyxovirus that infects more than 60% of children during the first year of life [1]
In order to select a challenge virus for a reliable and useful RSV human experimental infection model, children with RSV were first identified from an outpatient urgent care center, emergency department, or from the inpatient area of a large regional pediatric hospital in Memphis, TN
From the years 2000–2005, 288 patients without chronic underlying conditions under two years of age who tested positive for RSV by antigen detection (Binax and Directigen) were enrolled
Summary
Respiratory syncytial virus (RSV) is a paramyxovirus that infects more than 60% of children during the first year of life [1]. RSV Human Experimental Infection Model: Memphis-37 Challenge Virus therapeutic immunomodulatory agents, and other antiviral drug strategies for the protection of vulnerable populations against RSV disease. RSV Memphis-37 was isolated from a child with bronchiolitis, characterized, and manufactured for use as a challenge virus in the adult experimental infection model.
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