Use of Optical In Vivo Imaging to Monitor and Optimize Delivery of Novel Plasmid-Launched Live-Attenuated Vaccines.

Plasmid-launched live-attenuated vaccines (PLLAV) are a modality of next-generation vaccines with the promise to combine the benefits of both (1) the potency of live vaccines and (2) the ease of production, quality control, and thermal stability of classical DNA vaccines. Using the live yellow fever 17D (YF17D) vaccine as paradigm, we establish a bioluminescence-based in vivo imaging approach that allows to rapidly monitor and optimize the dose and route of delivery of such PLLAV in a mouse model of YF17D immunization. Vaccine virus replication thus launched in the skin of vaccinated mice can be quantified by the light emitted, benchmarked to signals originating from a YF17D reporter virus and finally correlated to the induction of humoral immune responses to the yellow fever virus.