|
|
OUR IMMUNOTHERAPY PRODUCT PLATFORMS
Aduro has developed two distinct Listeria product platforms: live attenuated Listeria and Killed but Metabolically Active (KBMA) Listeria.
- Live Attenuated Listeria Vaccines: In its wild-type form, Listeria can be a human pathogen. Aduro has deleted from the wild-type two genes required for pathogenicity, but not for immunogenicity. The actA deletion blocks the ability of Listeria to spread from cell to cell. The inlB deletion blocks the direct uptake of Listeria by hepatocytes, thus minimizing the potential to cause liver-related toxicity. Together, these deletions decrease virulence by more than 1,000-fold in mice and enable the safe administration of Listeria to humans. Importantly, this attenuated strain is as potent as wild-type Listeria at inducing T cell immune responses.
- Killed But Metabolically Active Listeria Vaccines: KBMA vaccines combine the safety of a killed vaccine with the potency of a live vaccine. Since the time of the polio virus vaccine, a balance has been sought between the use of live vaccines (better potency) versus killed vaccines (better safety). The KBMA vaccine platform kills the Listeria by virtue of random but infrequent DNA crosslinks in a Listeria strain that is engineered to be unable to remove or repair these crosslinks. Because of the impaired DNA repair mechanism, the number of crosslinks required to kill the bacterium is low enough that virtually all of its genes can still be expressed (activating innate immunity and expressing antigens for presentation to T cells); yet the bacterium cannot multiply because its DNA cannot separate into daughter strands. KBMA vaccines are ideal for use in prophylactic vaccination and for patient populations where the underlying risk from the disease is low.
|