The Science is There: Key Considerations for Stabilizing Viral Vector-Based Covid-19 Vaccines

Abstract

Once Covid-19 vaccines become available, 5e10 billion vaccine doses should be globally distributed, stored and administered. In this commentary, we discuss how this enormous challenge could be addressed for viral vector-based Covid-19 vaccines by learning from the wealth of formulation development experience gained over the years on stability issues related to live attenuated virus vaccines and viral vector vaccines for other diseases. This experience has led eover timee to major improvements on storage temperature, shelf-life and in-use stability requirements. First, we will cover work on 'classical' live attenuated virus vaccines as well as replication competent viral vector vaccines. Subsequently, we address replication deficient viral vector vaccines. Freeze drying and storage at 2e8 C with a shelf life of years has become the norm. In the case of pandemics with incredibly high and urgent product demands, however, the desire for rapid and convenient distribution chains combined with short end-user storage times require that liquid formulations with shelf lives of months stored at 2e8 C be considered. In confronting this "perfect storm" of Covid-19 vaccine stability challenges, understanding the many lessons learned from decades of development and manufacturing of live virus-based vaccines is the shortest path for finding promising and rapid solutions.

Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

“…However, it is not known if the lyophilization process itself will impact the potency and efficacy of the COVID-19 mRNA vaccines. Alternative drying processes, such as spray drying, foam drying, spray-freeze drying, vacuum drying, and supercritical fluid drying have been successfully employed to improve stability of biopharmaceutical formulations, including vaccines [ 55 , 56 ], which could also have the potential to improve stability of mRNA vaccines.…”

COVID-19 pandemics Stage II – Energy and environmental impacts of vaccination

“…There are different estimations for the emergent need for vaccination. Crommelin et al [ 28 ] estimated that the 5–10 × 10 9 vaccine doses are required for global distribution. The DHL Express team claimed around 1 × 10 10 vaccine doses are needed over the long term [ 29 ].…”

“…unavoidable wastage and unnecessary vaccine wastage [ 98 ]. From the perspective of historical experience, the stabilisation of vaccination relies on shelf-life, storage temperature and in-use stability [ 28 ]. The preventable wastage of COVID-19 vaccines may occur at different stages, mentioning at least a few: The massive purchase orders in the planning stage: Vaccine acceptance in different regions present heterogeneity [ 25 ].…”

A Comprehensive Overview on COVID-19: Future Perspectives

“…Viral vector-based vaccines: Viral vector vaccines employ live viruses to convey DNA into host cells for synthesizing antigenic proteins that can further be tailored to trigger the range of immune responses, especially the production of antibodies, cytotoxic T lymphocytes, T-helper cells, etc. ( Crommelin et al., 2021 ). In other words, such vaccines generally embody live attenuated viruses which can genetically be engineered to carry DNA encoding antigens (protein) from a different organism ( Crommelin et al., 2021 ).…”