Developing a respiratory syncytial virus (RSV) nanoparticle vaccine 9430

Description Respiratory syncytial virus (RSV) is a contagious virus that infects the respiratory tract. In the US, RSV is the top cause of respiratory disease in children & older adults. The viral envelope G glycoprotein, or RSV G, contains two heavily glycosylated mucin-like regions flanking an unglycosylated, highly conserved region called the central conserved domain (CCD). RSV G CCD interacts with human chemokine receptor CX3CR1 to promote infection in airway epithelial cells. Additionally, RSV infected cells secrete soluble G, which contributes to pathogenesis. The high sequence conservation of RSV G CCD, its interaction with a key receptor, & its role in pathogenicity make RSV G a prime vaccine target. However, RSV G-based vaccines have previously shown to be poorly immunogenic & recapitulate aspects of vaccine enhanced disease (VED). In this work, we developed & evaluated RSV G nanoparticle vaccines. We used a self-assembling nanoparticle platform displaying RSV G CCD to increase immunogenicity, & we introduced point mutations in RSV G CCD to mitigate VED in mice. Electron microscopy reveals that the nanoparticles are intact & homogeneous. Antibody binding studies show that the nanoparticles display RSV G CCD conformational epitopes. Vaccine studies in mice are currently underway. By using nanoparticle technology & strategic point mutations, we aim to overcome historical challenges in utilizing RSV G as a vaccine antigen & support the development of next-generation RSV vaccines. Funding Sources NIH R01 AI166066 Topic Categories Vaccines and Immunotherapy (VAC)