'Just break the glass’ — Inside CEPI’s 100-day plan for a new vaccine

The timeline for the development of the COVID-19 vaccine was unprecedented: just 326 days from the sequencing of the coronavirus until the first jabs received emergency use authorization. Now experts at the Coalition for Epidemic Preparedness Innovations believe they can slash that window by more than two-thirds.

CEPI, a global coalition launched in 2017 to develop immunizations against emerging infectious diseases, is spearheading an effort that would facilitate the development of a vaccine against an emerging disease in 100 days.

To deliver on that goal, though, will require resolving a “giant jigsaw puzzle” of interlinked challenges, as Dr.  Melanie Saville, CEPI’s executive director of vaccine research and development, described it at a March fundraising event for the initiative. That includes improving disease surveillance systems, creating an unprecedented vaccine library, and building truly global manufacturing capacity.

Within CEPI, efforts are already underway to lay early groundwork toward the 100-day strategy, even as the alliance looks to “inspire others to focus on the 100-day mission as a shared global goal,” Richard Hatchett, CEPI’s executive director, told Devex.

As an outsider to CEPI’s initiative, but an expert on infectious disease responses as the senior director of the System-wide Special Pathogens Program at NYC Health + Hospitals, Syra Madad said “having a goal of developing a vaccine in 100 days is absolutely possible with financial support, political will and some of the world’s best talent.”

The 100-day timeline was formulated within CEPI and gained traction during the United Kingdom’s 2021 G-7 presidency, which spotlighted a pathway for developing “safe, effective diagnostics, therapeutics and vaccines at scale and ready to be deployed equitably.” That vision was integrated into CEPI 2.0, the alliance’s five-year strategy released in November last year.

The plan

The details of what would actually happen within those 100 days is now coming into sharper focus.

Dedicated surveillance systems would detect the emergence of a disease, triggering standard containment measures. At the same time, the disease could be quickly sequenced to identify whether it is something previously unseen and, if so, trigger vaccine development.

That development would rely on a vaccine library, a collection of vaccine candidates drawn from the roughly 25 viral families. While it would be unreasonable to develop vaccines for all known viruses — and impossible to develop immunizations for those that remain unknown — “what you hope is that in your vaccine library, you may have multiple candidate vaccines or prototype vaccines” from each family, Hatchett said.

Researchers would then be able to identify prototypes that are “cousins” of the emerging disease, allowing them to skip the time-consuming step of identifying what part of the virus elicits an immune response. Instead, they would focus on tailoring the vaccine to the specific pathogen.

With the prototypes built to leverage rapid-response technologies, including messenger RNA, candidate vaccines could be rapidly developed. And because scientists would be able to rely on safety data and establish proof of efficacy from the prototype vaccines, they could then manufacture the candidates and shuttle them into clinical trials.

“You just break the glass and start the clinical trial as soon as the clinical trial material is released,” Hatchett said.

If the trials were essentially on standby, they could be stood up rapidly, with the first and second phases — to determine dosing and efficacy — potentially combined.

“There are a lot of opportunities for acceleration,” Madad said. “We’re able to eliminate a lot of that downtime, a lot of that waiting game of seeing if something is done before proceeding to the next step.”

Regulators, relying on those findings and existing information on expected immune protection drawn from already existing research, might then sanction emergency use of the new formulation for high-risk groups, even as large-scale clinical trials continue.

What needs to be done now

It will take far more than 100 days to be able to transform the 100-day mission into reality, though.

 “The other critical piece to the 100-day goal is a lot of the work has to be done in advance of a new pathogen emerging,” Hatchett said.

That includes building the vaccine library. CEPI has suggested it will prioritize the development of libraries for 10 of the virus families, with 10 to 15 vaccine candidates for each. That leaves at least 15 other virus families for partner organizations to explore.

There is also work to be done developing and building out the rapid development platforms and preenrolling clinical trials. And there is the extensive work of realigning regulatory systems, which will be critical to hitting the 100-day target. Regulators will need to be familiarized with the technology and research findings to ensure they are comfortable making quick decisions for the emergency use of newly developed vaccines.

The process may not be standard, but it is also not entirely unfamiliar. Hatchett compared it to the one used to create annual seasonal flu vaccines.

“It’s not like we don’t already do this,” he said. “It’s a novel application of an existing concept.” Though Madad said it was critical that the broader public was simultaneously brought along to ensure their acceptance of any vaccine that emerged.

“We have to be able to communicate the scientific process to individuals whenever it’s an accelerated timeline or innovative timeline,” she said. “It has to be communicated really methodically and in a way people understand.”

Mohga Kamal-Yanni, an adviser to the People’s Vaccine Alliance, said it was imperative that CEPI and others not lose sight of their promise of equitable access.

“I do believe they’re genuine in saying they’re prioritizing equitable access and that it’s not just a headline,” she told Devex. “How you are going to ensure that it happens is very, very important. What accountability mechanisms will be in place?”

That includes distributed manufacturing, which is integrated into CEPI’s 100-day vision. CEPI is already partnering with Institut Pasteur de Dakar to build a regional manufacturing hub for COVID-19 and other vaccines in Senegal’s capital Dakar and is looking for other partners capable of collaborating on vaccine development and manufacture.

Kamal-Yanni is looking for additional steps, including better integration of researchers from low- and middle-income countries in the actual innovation process, guarantees of information sharing about any vaccines that are developed, and transparency on agreements and contracts that are struck.

Finding partners

Meanwhile, CEPI is already at work trying to gather the other pieces that will make the 100-day goal a reality. The alliance has put out calls to fund partners who can develop RNA vaccine platform technologies and a vaccine library. But while the alliance can drive the effort, it will not be able to manage — or pay for — all of the different components that are needed to make the goal a reality.

“This is not something that gives CEPI a bunch of money and CEPI can go off and deliver for the world,” Hatchett said. Instead, he said it is about prioritizing specific initiatives but also encouraging national agencies and regional preparedness efforts to align their work with the 100-day goal.

He said the support is there, both for the global vision and also CEPI’s specific component. The alliance, however, was only able to raise just over $1.5 billion against its $3.5 billion budget for CEPI 2.0 during a March replenishment event.

Hatchett told Devex that CEPI never expected to achieve all five years of financing immediately and is “in line of sight” to have two-thirds of its funding lined up.

“But I'm even more encouraged by the emerging global consensus around the 100 days,” he said.

Update, April 29, 2022: This article has been updated to say that the 100-day timeline was first formulated within CEPI.