Martin L. Moore, PhD
Director, Children’s Center for Childhood Infections and Vaccines
Division of Infectious Disease
Department of Pediatrics
Emory University School of Medicine
Children’s Healthcare of Atlanta Research Scholar
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, viral pneumonia, and viral death in infants, both in the USA and worldwide. RSV causes an estimated 300 infant deaths per year in the USA and 200,000 infant deaths worldwide. Approximately 1% of the infant cohort in the USA is hospitalized due to RSV infection each winter. Airway mucus is a hallmark of RSV lower respiratory tract infection. Mucus, necrotic epithelial cell debris, and inflammatory cells obstruct the airways, leading to characteristic wheezing and respiratory failure in severe cases. There is no RSV vaccine in use and no proven antiviral therapy. A prophylactic RSV neutralizing antibody, palivizumab, which targets the fusion (F) protein, is given to high-risk infants. However, palivizumab carries a staggering monetary health care cost to prevent RSV-related hospitalization.
The goals of my research program are to elucidate molecular mechanisms of RSV pulmonary pathogenesis and to advance RSV vaccines and antivirals. We developed two model systems that synergistically enable these goals: a mouse model of RSV pathogenesis that recapitulates some features of RSV bronchiolitis and an efficient RSV reverse genetics system.
The mouse model of RSV pathogenesis we developed is based on relatively pathogenic and “mucogenic” RSV strains. These are useful for studying molecular mechanisms of RSV pathogenesis leading to airway pathology and lung dysfunction, and they are useful as challenge strains to test the efficacy of experimental RSV antivirals and vaccines in mice. Our current focus is on the role of the RSV fusion (F) protein in pathogenesis.
We are using the RSV reverse genetics system to develop novel live attenuated RSV vaccine candidates. Due to safety issues with inactivated and subunit RSV vaccines in infants, live attenuated RSV vaccines are the most clinically advanced in pediatric populations. However, current live attenuated RSV vaccine candidates suffer from genetic instability (reversion of attenuating mutations) and relatively low immunogenicity. Our goal is to genetically manipulate RSV to achieve attenuation with genetic stability and enhanced immunogenicity. Along the way, we developed a number of RSV research reagents, RSV strains, and tools to foster collaboration with industry and academic groups.