Live-attenuated RSV Vaccines: An RNA Based Approach to Attenuate Virus Replication
Daisy Leung, Ph.D.
Pathology and Immunology
Center for Pediatric Pulmonary Disease
Interdisciplinary Research Initiative
2/1/2018 - 1/31/2021
Kristine Wylie, Avraham Beigelman
Respiratory syncytial virus causes more than 30 million new episodes of acute respiratory tract infection in children under five with 3.4 million hospitalizations and between 66,000 and 199,000 deaths each year. Despite this impact, no licensed RSV vaccine is available. Here, we propose to develop candidate live- attenuated RSV vaccines using a new research platform that was developed and validated for influenza virus. State-of-the-art sequencing technologies will identify critical RNA structures in the genome of RSV. These RNA structures will be modified resulting in mild to severe attenuation of the virus. This approach is superior over previous candidate live-attenuated RSV vaccines because (i) it preserves all immune cell epitopes and (ii) the level of attenuation can be tuned to create both a safe and immunogenic vaccine. To develop the candidate live-attenuated RSV vaccines we propose the following two aims:
Proposed specific aims
· Define the RNA structures in the genome of RSV.
· Determine which RNA structures in the genome are critical for RSV replication.
Potential impact on child health
A vaccine for RSV will greatly reduce the number of hospitalizations and deaths associated with RSV infections in young children.