Critical Path to First-in-Human Batches of ChAdOx Vectors, Including for Emergency Response.

Background

Adenovirus-vectored vaccines played an important role in the global response to SARS-CoV-2. Adenovirus platforms have many advantages including a simple and readily transferred manufacturing process, low cost, and thermostability. Speed of production of an initial Good Manufacturing Practice (GMP)-compliant batch has, however, been viewed as a limitation of adenovirus vectors relative to mRNA platforms. Production of the initial viral starting material and release testing are key rate-limiting steps.

Methods

Production of viral starting material from DNA, and release testing in accordance with regulatory expectations, for first-in-human trials of adenovirus-vectored vaccines.

Results

We describe experience of these stages in the production of the first GMP batches for multiple adenovirus-vectored candidates and the adaptations made for ChAdOx1 nCoV-19 (the Oxford COVID-19 vaccine) in early 2020. We also report development of a streamlined approach to starting material generation, enabling initial GMP batch availability within c. 60 days of publication of a new pathogen sequence. Using a New World arenavirus vaccine construct as a proof of concept, we demonstrate reproducible execution of this pipeline, maintaining acceptable infectivity and other quality attributes.

Conclusions

We discuss opportunities for additional time savings in the future. This work demonstrates suitability of an adenovirus platform to contribute to the "100 Days Mission" for vaccines against "Disease X".