According to a journal report published by members of the Coalition for Epidemic Preparedness Innovation (CEPI) this week, SARS-CoV-2 — the virus which causes COVID-19 — uncovers the advances and ongoing stumbling blocks in vaccine development.
Other outbreaks and epidemics have helped lead to a time of advancement in basic scientific understanding, and the virus has spurred the development of multiple platforms.
“Vaccine development is a lengthy, expensive process,” the authors wrote. “Attrition is high, and it typically takes multiple candidates and many years to produce a licensed vaccine. Because of the cost and high failure rates, developers typically follow a linear sequence of steps, with multiple pauses for data analysis or manufacturing-process checks. Developing a vaccine quickly requires a new pandemic paradigm, with a fast start and many steps executed in parallel before confirming a successful outcome of another step, hence resulting in elevated financial risk.”
Now is a time of DNA and RNA-based platforms that allow vaccines to be made quickly through synthetic processes. Build times could be cut still further with the use of next-generation sequencing and reverse genetics. Plus, regulators are experienced with reviewing such technologies. The parts are there to speed things along, but there are always concerns.
Take the SARS-CoV-2 vaccine development, specifically. Even with novel platforms in play, and a promising immunogen for protection, the optimal antigen design that could ensure optimal immune response is debated. Further, preclinical experience with other coronavirus vaccine candidates have revealed the potential to exacerbate lung disease while trying to help, making safety monitoring critical, along with data and careful regulatory reviews. Even with SARS and MERS as predecessors to COVID-19, any correlating protections between them are not yet established, nor is the potential duration of immunity from single-dose vaccines.
CEPI is currently supporting the development of vaccines against five epidemic pathogens on the World Health Organization’s priority list, along with platform technologies to prepare for emerging epidemic diseases like COVID-19. Ideally, the authors note, such a platform could support development from viral sequencing to clinical trials in less than four months and have vaccines ready to go for large-scale manufacturing, but the ideal rarely lines up.
For some of the current candidates, additional clinical trial material for phase 2 studies is being manufactured, but proceeding rapidly beyond phase 2 trials means, according to the CEPI authors, that manufacturing will need to be scaled up to commercial levels before substantial safety and immunogenicity data are available. Building such capacity can take millions of dollars. For novel platform technologies, facilities even capable of producing large quantities of product would need to be identified, the technologies transferred to them and manufacturing processes adapted to the challenge — and that’s without any guarantees the vaccine will be usable.
“It’s far from certain that these new platforms will be scalable or that existing capacity can produce sufficient quantities of vaccine fast enough,” the authors wrote. “It’s therefore critical that vaccines also be developed using tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
Further, in an ongoing pandemic, the authors warn that it is difficult to predict where and when the next outbreak will occur and prepare trial sites accordingly. Multiple vaccines also can’t be allowed to crowd one another, as was seen with Ebola therapeutics during the 2013-2016 outbreak of that disease. And as deaths mount, as they are with COVID-19, the authors note the general population must be considered, as it may not accept randomized, controlled trials with placebo groups. Adaptations can be made, but such approaches can prove complex, and developers tend to avoid trials that generate head-to-head comparative data.
CEPI is trying to find the best way forward for everyone, but as yet, no easy answer or solution remains. A global system would help, but one is not currently in place for worldwide allocation.
Contributors to the CEPI article included Drs. Nicole Lurie, Melanie Saville, Richard Hatchett, and Jane Halton.