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

Area of Science:

• Vaccinology
• Viral Vector Technology
• Biologics Manufacturing

Background:

• Adenovirus-vectored vaccines are crucial for global health security, offering advantages like cost-effectiveness and thermostability.
• Historically, the speed of initial Good Manufacturing Practice (GMP) batch production was a limitation for adenovirus platforms compared to mRNA.
• Key bottlenecks in adenovirus vaccine production include viral starting material generation and release testing.

Purpose of the Study:

• To describe the production of viral starting material and release testing for adenovirus-vectored vaccines.
• To report adaptations for ChAdOx1 nCoV-19 (Oxford COVID-19 vaccine) production.
• To present a streamlined approach for rapid GMP batch availability.

Main Methods:

• Production of viral starting material from DNA.
• Implementation of release testing aligned with regulatory standards.
• Validation of a streamlined pipeline using a New World arenavirus vaccine construct.

Main Results:

• Successful production of initial GMP batches for multiple adenovirus-vectored vaccine candidates.
• Adaptations were made for ChAdOx1 nCoV-19 production in early 2020.
• A streamlined approach enabled GMP batch availability within approximately 60 days of pathogen sequence publication.
• The pipeline demonstrated reproducible execution with acceptable infectivity and quality attributes.

Conclusions:

• Adenovirus platforms can be rapidly scaled for vaccine production, supporting global pandemic preparedness.
• Further optimizations can reduce production timelines for adenovirus-vectored vaccines.
• This work supports the suitability of adenovirus vectors for the '100 Days Mission' against 'Disease X'.