University of Minnesota (UMN)
By: Jim Wappes
January 17, 2017
In its third report in as many years, a team of vaccine, public health, and industry experts today urge global leaders to not let up on developing as many Ebola vaccines as needed so the world will be better prepared for the next outbreak of the deadly disease, even though public attention has shifted to other threats, including Zika virus.
The "Team B" panel of experts, in its "Completing the Development of Ebola Vaccines" report, commends the World Health Organization (WHO) for its leadership in response to the 2013-16 West Africa outbreak, but calls for new, innovative ways to keep momentum going and bring one or more vaccines to regulatory approval, which has yet to happen. The WHO was roundly criticized for its slow response to Ebola, and the authors of the report say the agency "is not in a position to manage and fund all of the complexities associated with bringing Ebola vaccines to market." Instead, they recommend a separate "champion" group to see vaccine and preparedness efforts come to fruition, with input and guidance from the WHO.
The report highlights the impressive achievement of quickly producing and obtaining favorable results in humans for one vaccine, Merck's rVSV-ZEBOV. Yet it emphasizes that not only has that vaccine not been licensed, but many questions remain about how to move forward with that and other vaccines and how best to position global health to arm itself for the next infectious disease threat.
"We must maintain the sense of urgency that has pushed this work forward in previous years," said Jeremy Farrar, MD, PhD, Wellcome Trust director and Team B co-chair. "The success of future efforts will depend on our continued action with the Ebola vaccine, and we call on the global community to commit to overcoming the remaining hurdles."
The expert panel, called Ebola Vaccine Team B, was assembled in 2014 by the Wellcome Trust and the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The "Team B" moniker refers to its supportive role to the WHO and other leadership agencies.
"We clearly have made important progress with realizing effective Ebola vaccines that can one day result in an Ebola-prepared world. But I worry that we're currently trying to power this Ebola vaccine train with an automobile engine," said CIDRAP Director Michael Osterholm, PhD, MPH, the other Team B co-chair. "There are critical challenges that remain with regard to vaccine R&D [research and development], licensing, financing and both outbreak and prophylactic deployment."
CIDRAP is the publisher of CIDRAP News, but its research and policy efforts operate independently from its news operations.
Team B published "Recommendations for Accelerating the Development of Ebola Vaccines: Report and Analysis" in February 2015 and "Plotting the Course of Ebola Vaccines: Challenges and Unanswered Questions" in March 2016.
Gaps in Ebola vaccine readiness
The report lists 13 key gaps in moving forward with vaccine candidates and in overall Ebola vaccine preparedness, including stalling out on decisions necessary to license rVSV-ZEBOV. Other uncertainties surround the planning about vaccine stockpiling, how to be ready to conduct further vaccine trials when the next outbreak occurs, how to reimburse manufacturers, and the fate of other vaccine candidates once Merck's vaccine is licensed.
Since its inception, Team B has emphasized that, even if one vaccine gains licensure, there could well be a role for other vaccines that demonstrate benefits in other ways, such as storage at more convenient temperatures or length of immune response.
The WHO has lagged on making some key vaccine-related decisions, the experts write. "The WHO has not made determinations regarding the Emergency Use Assessment and Listing (EUAL) applications for Ebola vaccines from Merck (filing completed in December 2015) and Johnson & Johnson (filing completed in September 2016)." The WHO developed the EUAL designation to expedite vaccine candidates.
The report adds, "Coordination of approvals for emergency use of vaccines remains a gap in preparedness against Ebola. For example, the WHO needs to clarify how vaccines with EUAL status will be granted approval for emergency use by local national regulatory authorities (NRAs). Ideally, a harmonized emergency use regulatory pathway across regulatory agencies should be in place." At the moment, it is not.
The Team B report also details challenges for vaccines that are not rVSV-ZEBOV, as the outbreak in West Africa was dwindling when they were ready for large-scale trials. The experts also enumerate overarching problems that any vaccine maker faces.
In addition, global health leaders are faced with vastly reduced interest in Ebola once the outbreak was declared over last year. "Part of the challenge we have is that the world looks at what happened in West Africa in 2013 through 2016 with Ebola as a one-off event," Osterholm said. "I worry about what could happen if an outbreak flares in a huge metropolitan area like Kinshasa [of the Democratic Republic of the Congo]. That outbreak could dwarf anything we've seen in the past."
Foremost among the group's 11 recommendations is restructuring of leadership for Ebola vaccine preparedness.
"Consideration should be given," the group writes, "to establishing a dedicated consortium focused on 'championing' Ebola vaccines and resolving the remaining key issues related to global Ebola emergency preparedness (similar to what has been done with meningococcal and malaria vaccine initiatives). This group could represent a new public-private partnership that would operate independent of the WHO, but with WHO input and guidance."
Such a group would be able to spearhead strategies to address the gaps raised in the report, the experts say.
Osterholm added that having three key leadership positions in transition in 2016—the WHO director-general, the United Nations secretary general, and the president of the United States—adds another layer of complication to the leadership issue. He said Ebola vaccine efforts need champions in all three positions in order to advance.
He added that the newly formed Coalition for Epidemic Preparedness Innovations (CEPI) could also play a key role. CEPI was initiated in August 2016 and includes stakeholders from governments, industry, public and philanthropic funders, academia, and other groups.
Team B member David Kaslow, MD, vice president of essential medicines for the global health nonprofit PATH, underscored the need for a novel public-private partnership in outbreak response.
"No one existing entity encompasses the critical contributors needed for an optimal comprehensive response. . . . As such, either a significant change in the terms of reference of an existing entity or a new, inclusive entity will be needed. Despite all the complexities associated with standing up a new entity, such as CEPI, a new public-private partnership is likely the best approach."
Other recommendations in the report center on hurdles that vaccine manufacturers face; promotion of scientific collaboration; exploration of using vaccines for people at high risk, such as healthcare workers, before an outbreak occurs; clarification of steps for regulatory approval; planning for additional clinical trials; and development of strategies for post-licensure trials.
Future role for Team B
The work of Team B will continue as long as there is a need for a catalyst to keep Ebola vaccine efforts—and infectious disease preparedness in general—advancing, Osterholm said.
"Team B will continue to play, I hope, a critical role. We are committed to staying the course until we have a world prepared for Ebola."
Kaslow added, "The time-tested Red Team approach of an independent, multidisciplinary team, embodied by Team B, to poke holes and provocatively prod well-established organizations to challenge conventional wisdom or group think, will no doubt sharpen the focus of responses and generate innovative solutions to future outbreak responses and preparedness.
"A standing Team B to provide real-time poking and prodding is a prudent insurance policy for being better prepared for responding to the next outbreak."