Bacterial artificial choromosome (BAC) plasmid containing the antigenomic sequence of RSV that can be used for directed mutations of the virus and thus vaccine generation.
- Viral DNA is contained in a BAC, Allowing for efficient mutagenesis and recombineering of viral DNA.
- BAC is stable, can be used for cloning in common bacteria types like E. Coli.
- Provides powerful tool for vaccine developers to use in engineering potential RSV vaccines.
Human RSV is a leading cause of respiratory infections in the US leading to over 100,000 infant hospitalizations annually, and 160,000 deaths globally per year. Beyond infants, RSV-related illnesses in the elderly are on the rise, affecting approximately 5 -10% of nursing home patients, and accounting for around 10,000 deaths. As the population ages, these numbers are expected to continue growing. Currently, the only prophylactic intervention available is a monoclonal antibody-based therapy which must be administered repeatedly, and does not provide lasting resistance to the virus; when treatment is stopped, immune protection fades. Given these shortcomings and the fact that RSV infections impact particularly vulnerable populations, the generation a vaccine strategies for tackling the virus are needed.
The primary focus of Dr. Moore?s lab at Emory is to define mechanisms of RSV immunopathogenesis and investigate the role of RSV strain differences in RSV pathophysiology. Dr. Moore and colleagues have created a bacterial artificial chromosome (BAC) containing the complete antigenomic sequence of RSV. This BAC has been engineered to contained improvements over current RVS plasmids including multiple restriction sites for easy manipulation as well as changes to the ribozyme sequences which would control production of the virus. These improvements enable researchers to potentially target mutations of RSV and improve the attenuation and immunogenicity of the virus leading to stable mutants for effective more vaccine design and development.
BAC has been created and used in in vitro work.