Stable Attenuation of Human Respiratory Syncytial Virus for Live Vaccines by Deletion and Insertion of Amino Acids in the Hinge Region between the mRNA Capping and Methyltransferase Domains of the Large Polymerase Protein

• DOI: 10.1128/jvi.01831-20
• Publication Date: 2020-09-29T13:55:10Z
• Authors: Miaoge Xue; Rongzhang Wang; Olivia Harder; Phylip Chen; Mijia Lu; Hui Cai; Anzhong Li; Xueya Liang; Ryan Jennings; Krista La Perle; Stefan Niewiesk; Mark E. Peeples; Jianrong Li
• Keywords: Attenuated vaccine

Human respiratory syncytial virus (RSV) is the leading viral cause of lower tract disease in infants and children worldwide. Currently, there are no FDA-approved vaccines to combat this virus. The large (L) polymerase protein RSV replicates genome transcribes mRNAs. L organized as a core ring-like domain containing RNA-dependent RNA an appendage globular domains mRNA capping region cap methyltransferase region, which linked by flexible hinge region. Here, we found that tolerant amino acid deletion or insertion. Recombinant RSVs carrying single double alanine insertion were genetically stable, highly attenuated immortalized cells, had defects replication spread, delay innate immune cytokine responses primary, well-differentiated, human bronchial epithelial (HBE) cultures. these recombinant viruses was upper tracts cotton rats. Importantly, elicited high levels neutralizing antibody provided complete protection against replication. Taken together, deletions insertions can serve novel approach rationally design attenuated, immunogenic live vaccine candidates for RSV.IMPORTANCE Despite tremendous efforts, (RSV). A one most promising strategies RSV. However, it has been challenge identify strain optimal balance between attenuation immunogenicity. In study, generated panel sufficiently grow titer cultured while retaining Thus, may be