Novel respiratory syncytial virus challenge strain identified in human infection trial
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A novel respiratory syncytial virus strain led to infections in all but one of 20 healthy adults in a controlled human infection trial designed to evaluate the safety and infectious potential of the strain.
The findings were presented during the 2020 Virtual Annual Conference on Vaccinology Research sponsored by the National Foundation for Infectious Diseases.
“Controlled human infection studies allow us to quickly evaluate a potential vaccine or therapeutic to see if they are likely to work before a large phase 3 trial is done. This helps to down-select candidates and only take those candidates most likely to be effective into large efficacy trials,” Kawsar R. Talaat, MD, assistant professor at Johns Hopkins Bloomberg School of Public Health, told Healio. “This will allow faster development of products that are promising and spare the time, exposure to individuals and resources involved in large trials from products that are less likely to be effective.”
According to Talaat, respiratory syncytial virus remains a pathogen for which effective vaccines and therapeutics are “desperately needed.” In addition, promising candidate vaccines and therapeutics are often taken into large phase 3 trials only to demonstrate a lack of efficacy, she continued.
“While human challenge models have been conducted against RSV, there is no challenge strain available in the United States,” Talaat said. “This study aims to evaluate an RSV challenge strain for use in the U.S. by looking at the safety and infectivity of rRSV A/Maryland/001/11, a new recombinant strain.”
Talaat and colleagues recruited and enrolled 20 healthy nonpregnant adults aged 18 to 50 years with prechallenge serum RSV neutralizing antibody titers in an open-label, phase 1 study designed to examine the safety, infectivity, replication and immunogenicity of rRSV A/Maryland/001/11. The researchers administered 105 plaque-forming units of rRSV A/Maryland/001/11 intranasally and monitored patients for adverse events.
Overall, 15 (75%) of participants experienced respiratory symptoms, most commonly nasal congestion and nasal mucosal erythema, rhinorrhea, sneezing, coughing and middle ear effusions. Most symptoms were mild.
According to the study results, 19 of 20 volunteers had virus detectable by RT-qPCR on Day 1 after challenge, whereas nine had virus detectable by immunoplaque assay. All participants were culture negative for RSV by Day 11 after challenge.
The baseline geometric mean neutralizing antibody titer was 6.5 log2 (standard deviation, 0.9), which increased to 7.4 log2 (standard deviation, 1) on Day 28 after challenge and 7.5 log2 (standard deviation, 0.9) on Day 56.
“In this pilot study, the rRSV A/Maryland/001/11 virus was shown to be infectious, with 95% of the volunteers having virus detected by PCR. The virus also caused mild to moderate upper respiratory symptoms in the volunteers,” Talaat said. “This is a potential challenge strain for RSV and further development needs to be discussed.”
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Talaar K, et al. Development of a novel respiratory syncytial virus controlled human infection mode: Phase 1 study of rRSV A/Maryland/001/11 in healthy adult volunteers. Presented at: NFID Annual Conference on Vaccinology Research; June 18-19, 2020 (virtual meeting).
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