RSV is the leading cause of bronchiolitis, viral pneumonia, and viral death in infants. RSV is the leading cause of respiratory failure and mechanical ventilation in infants. There is no RSV vaccine in use and no widely available therapies. RSV is not only a scourge of infancy but also a major cause of asthma exacerbations in children and adults, and a major cause of pneumonia in the elderly. Airway mucus is a hallmark feature 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. We identified and derived strains of RSV that exhibit differential disease phenotypes in mice. Some RSV strains induce high levels of the cytokine IL-13, airway mucus, severe histopathology, and pulmonary obstruction, whereas other strains induce a more protective TH1-type response.
HRV and RSV are the leading causes of the common cold. Each presents different challenges for a safe and effective vaccine. We are working to bring several vaccine candidates through clinical trials, in addition to researching new vaccine candidates and methods. This pairs well with the second main aim of my lab, to define mechanisms of RSV immunopathogenesis and investigate the role of RSV strain differences in differential RSV pathophysiology.
We use differentially virulent RSV strains, and a novel RSV reverse genetics system we developed, to dissect molecular mechanisms leading to airway mucus expression, bronchiolitis, and pulmonary obstruction in the mouse model. These studies led to our current vaccine candidates, and will hopefully lead to additional effective vaccines and/or therapies for RSV disease. A comprehensive understanding of how RSV strain differences affect pathogenesis and immunity will require bridging gaps between basic research, epidemiology, and clinical studies.
- Dr. Sujin Lee, Asst Professor
- Dr. Christina Rostad, Instructor
- Michael Currier, Lab Manager
- Dr. Stacey Human, Post Doctoral Fellow
- Dr. Barbara Schlingmann, Post Doctoral Fellow
- Sean Todd, Research Specialist
- Carla Shoffeitt, Histotechnologist
- A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation. Stobart CC, Rostad CA, Ke Z, Dillard RS, Hampton CM, Strauss JD, Yi H, Hotard AL, Meng J, Pickles RJ, Sakamoto K, Lee S, Currier MG, Moin SM, Graham BS, Boukhvalova MS, Gilbert BE, Blanco JC, Piedra PA, Wright ER, Moore ML. Nat Commun. 2016 Dec 21;7:13916. doi: 10.1038/ncomms13916.
- A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques. Lee S, Nguyen MT, Currier MG, Jenkins JB, Strobert EA, Kajon AE, Madan-Lala R, Bochkov YA, Gern JE, Roy K, Lu X, Erdman DD, Spearman P, Moore ML. Nat Commun. 2016 Sep 22;7:12838. doi: 10.1038/ncomms12838.
- A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats. Rostad CA, Stobart CC, Gilbert BE, Pickles RJ, Hotard AL, Meng J, Blanco JC, Moin SM, Graham BS, Piedra PA, Moore ML. J Virol. 2016 Jul 27;90(16):7508-18. doi: 10.1128/JVI.00012-16.
- EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression. Currier MG, Lee S, Stobart CC, Hotard AL, Villenave R, Meng J, Pretto CD, Shields MD, Nguyen MT, Todd SO, Chi MH, Hammonds J, Krumm SA, Spearman P, Plemper RK, Sakamoto K, Peebles RS Jr, Power UF, Moore ML. PLoS Pathog. 2016 May 6;12(5):e1005622. doi: 10.1371/journal.ppat.1005622.
- Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes. Stobart CC, Moore ML. Expert Rev Vaccines. 2015;14(12):1563-72. doi: 10.1586/14760584.2015.1095096. Review.
- Functional Analysis of the 60-Nucleotide Duplication in the Respiratory Syncytial Virus Buenos Aires Strain Attachment Glycoprotein. Hotard AL, Laikhter E, Brooks K, Hartert TV, Moore ML. J Virol. 2015 Aug;89(16):8258-66. doi: 10.1128/JVI.01045-15.
- Identification of residues in the human respiratory syncytial virus fusion protein that modulate fusion activity and pathogenesis. Hotard AL, Lee S, Currier MG, Crowe JE Jr, Sakamoto K, Newcomb DC, Peebles RS Jr, Plemper RK, Moore ML. J Virol. 2015 Jan;89(1):512-22. doi: 10.1128/JVI.02472-14.
- Refining the balance of attenuation and immunogenicity of respiratory syncytial virus by targeted codon deoptimization of virulence genes. Meng J, Lee S, Hotard AL, Moore ML. MBio. 2014 Sep 23;5(5):e01704-14. doi: 10.1128/mBio.01704-14.
- Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins. Lee S, Quan FS, Kwon Y, Sakamoto K, Kang SM, Compans RW, Moore ML. Antiviral Res. 2014 Nov;111:129-35. doi: 10.1016/j.antiviral.2014.09.005.
- RNA virus reverse genetics and vaccine design. Stobart CC, Moore ML. Viruses. 2014 Jun 25;6(7):2531-50. doi: 10.3390/v6072531. Review.
- The respiratory syncytial virus fusion protein and neutrophils mediate the airway mucin response to pathogenic respiratory syncytial virus infection. Stokes KL, Currier MG, Sakamoto K, Lee S, Collins PL, Plemper RK, Moore ML. J Virol. 2013 Sep;87(18):10070-82. doi: 10.1128/JVI.01347-13.