When I learned that an outbreak of Ebola was declared in Uganda last fall, I had a flashback to 2014 when I was working at Merck and an outbreak of Ebola disease caused by a different species of the virus emerged in full force in West Africa.
At the time, doses of a candidate vaccine against the virus circulating in West Africa had been developed and were in Merck’s freezers. In a collaboration with many external partners, we managed to test the vaccine in West Africa in a so-called ring vaccination trial: We identified individuals who likely had Ebola disease, then identified their contacts and their contacts’ contacts — establishing a social contact ring, or network — and offered the vaccine to individuals at greatest risk of exposure.
This trial demonstrated the efficacy of the vaccine candidate by July 2015, just 10 months after the first Phase 1 clinical trial started.
Nearly eight years later, was the global health community better prepared for the Uganda outbreak? Although the formation of the Coalition for Epidemic Preparedness and Response, and initiatives such as the World Health Organization’s R&D Blueprint and the global Covid-19 vaccine partnership COVAX, have led to important progress, I argue that there is still a long way to go.
As the Ebola outbreak escalated in October and November, the WHO worked with global health experts to evaluate and prioritize candidate vaccines targeting the virus circulating in Uganda. These vaccines were being developed by two nonprofits — the Sabin Vaccine Institute and IAVI, which I work for — and the University of Oxford. The WHO intended to include these candidates in a ring vaccination trial. (The vaccine tested in 2015, which was subsequently licensed, unfortunately does not work against the Ebola virus species spreading in Uganda.)
Among the three developers, an intense around-the-clock effort allowed one of the vaccine candidates to reach Uganda in a record 79 days after the outbreak was declared; the other two followed shortly after. Yet before the trial could begin, the comprehensive public health response in Uganda contained transmission of the virus. No new cases were reported after December 5, 2022, and the outbreak was officially declared over on January 11, 2023. The Ugandan Ministry of Health confirmed 142 cases of Ebola disease and 55 deaths.
Because of the brevity of this outbreak, it was not possible to evaluate vaccine candidates. With any infectious disease, the pathogen must be circulating to show that the vaccine prevents illness. In spite of the speed of this response, it wasn’t possible to get the vaccine candidate in country quickly enough to demonstrate its efficacy. Without showing that a vaccine works in a traditional efficacy trial, the path to licensing the product is much more complex: Without a licensed product, a vaccine cannot be rolled into a public health response to an outbreak, but may be used only in clinical trials.
If a well-managed stockpile of the unlicensed vaccine candidates that target the Ebola virus circulating in Uganda had already been established, the trials could have started earlier in the epidemic curve. This is the case for other diseases like Nipah and Middle East respiratory syndrome, for which no stockpile exists because there are no licensed vaccines.
The global public health community needs a mechanism for stockpiling yet-to-be-licensed vaccines across known viral families so they can be rapidly deployed in clinical trials during outbreaks. After the 2014-2016 West Africa Ebola outbreak and following the licensure in 2019 of the Merck Ebola vaccine, Ervebo, an International Coordination Group of four global health agencies developed a stockpile of that vaccine. This mechanism has been put in place to help any country facing that type of Ebola outbreak and is meant to protect people at highest risk of contracting the disease, including health care workers, front-line workers, and contacts of cases.
In 2021, health officials deployed the existing Ebola vaccine stockpile several times, releasing about 7,500 doses in response to Ebola outbreaks in the Democratic Republic of the Congo, demonstrating the usefulness of this type of mechanism. To date, it is only for licensed products. It’s now time to extend it to vaccine candidates or create something similar for products in development.
While the Coalition for Epidemic Preparedness and Response is funding a large portfolio of vaccines for many priority pathogens, forming stockpiles of these products in development should be a broader responsibility among of number of international organizations and will require both a tremendous amount of coordination and resources. It will be important to establish where the stockpiles are stored, who maintains them, how they are funded, and how decisions are made on their use.
Emerging infectious diseases are here to stay, and the number of outbreaks occurring each year is increasing given factors such as climate change, urbanization, aging populations with aging immune systems, increasing epizootic and spillover events, and increased migration and global travel. In 2022 alone, a public health emergency of international concern was declared for mpox, Marburg outbreaks occurred for the first time in Ghana and Guinea, exported cases of Lassa fever surfaced in the United Kingdom with documented secondary transmission, the first case of domestically acquired paralytic polio since 1970 occurred in the U.S., and worrisome SARS-CoV-2 variants continued to emerge. Yet outbreak response and preparedness are woefully underfunded, even after the collective global experience over the past three years as the Covid-19 pandemic vividly demonstrated how devastating, painful, and disruptive an emerging infectious disease can be.
Thankfully, the latest Ebola outbreak in Uganda is over. The question now is whether the global public health community will revert to its pattern of reacting to an emergency situation, coming together to fight the outbreak with enormous effort and genuine intent, and then reprioritizing efforts to other diseases as the outbreak subsides and funding shifts. Business as usual will not allow a better state of readiness in the global health security agenda, and communities and health systems will certainly not be better prepared if global health stakeholders don’t apply lessons learned from past epidemics in a more thoughtful and deliberate way.
Funders, governments, global health agencies, and nonprofit and for-profit product developers need to work together to muster adequate funding, resources, and innovative partnership models to collectively prepare in between outbreaks.
Swati Gupta is vice president and head of emerging infectious diseases and epidemiology at IAVI, a nonprofit scientific research organization that develops vaccines and antibodies for HIV, tuberculosis, emerging infectious diseases (including Covid-19), and neglected diseases. She reports owning Merck stock from when she was employed by that company.
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