Process development of a SARS-CoV-2 nanoparticle vaccine

• Published in: Process biochemistry (1991) 2023-06, Vol.129, p.241-256
• Main Authors: Martinez-Cano, Diandra, Ravichandran, Rashmi, Le, Huong, Wong, H. Edward, Jagannathan, Bharat, Liu, Erik J., Bailey, William, Yang, Jane, Matthies, Kelli, Barkhordarian, Hedieh, Shah, Bhavana, Srinivasan, Nithya, Zhang, Jun, Hsu, Angel, Wypych, Jette, Stevens, Jennitte, Piedmonte, Deirdre Murphy, Miranda, Les P., Carter, Lauren, Murphy, Michael, King, Neil P., Soice, Neil
• Format: Article
• Language: English
• Subjects: COVID-19; First-in-human; Nanoparticle vaccine; Process development; SARS-CoV-2
• ISSN: 1359-5113; 1873-3298
• DOI: 10.1016/j.procbio.2023.03.014

One of the outcomes from the global COVID-19 pandemic caused by SARS-CoV-2 has been an acceleration of development timelines to provide treatments in a timely manner. For example, it has recently been demonstrated that the development of monoclonal antibody therapeutics from vector construction to IND submission can be achieved in five to six months rather than the traditional ten-to-twelve-month timeline using CHO cells [1,2]. This timeline is predicated on leveraging existing, robust platforms for upstream and downstream processes, analytical methods, and formulation. These platforms also reduce; the requirement for ancillary studies such as cell line stability, or long-term product stability studies. Timeline duration was further reduced by employing a transient cell line for early material supply and using a stable cell pool to manufacture toxicology study materials. The development of non-antibody biologics utilizing traditional biomanufacturing processes in CHO cells within a similar timeline presents additional challenges, such as the lack of platform processes and additional analytical assay development. In this manuscript, we describe the rapid development of a robust and reproducible process for a two-component self-assembling protein nanoparticle vaccine for SARS-CoV-2. Our work has demonstrated a successful academia-industry partnership model that responded to the COVID-19 global pandemic quickly and efficiently and could improve our preparedness for future pandemic threats. [Display omitted] •Nanoparticle vaccine comprised of two subunits: Component A and Component B.•Generation of FIH material of Component A in support of clinical development.•Development and GMP manufacturing on an extremely accelerated timeline of 6 months.•Leveraged stable pool instead of clone reduces development timeline by 2–3 months.•A potential process platform to use across different Component A molecules.