Novel Ways to Advance Sudan Ebolavirus Vaccine Candidates? Experts Meet as Uganda’s Outbreak Declared Over Ebola 11/01/2023 • Elaine Ruth Fletcher Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Health workers in Mubende, Uganda, to test suspected Ebola cases shortly after an outbreak of the Sudan virus strain was first declared there in September, 2022. WHO’s Africa Region has declared the end to the recent outbreak of Sudan Ebolavirus – just a day before WHO convenes Ebola experts in a global consultation to explore a way forward on testing three candidate vaccines for the deadly Sudan strain of the virus. The oubreak was declared over after the elapse of 44 days since the discovery of the last case. That waiting period is double the 21-day period of time within which contacts of Ebola cases may become become ill with the deadly disease. Uganda’s relatively rapid and effective campaign against the outbreak – which began on 20 September 2022 – was celebrated by health authorities, who fought the virus with classic measures like contact tracing, case isolation and treatment – in the absence of a vaccine against the Sudan strain of Ebolavirus. GOOD NEWS! 🥳 Today, #Uganda 🇺🇬 declared the end of the Sudan #Ebola virus outbreak that erupted less than 4 months ago in the central Mubende district! Congratulations to national health authorities, health workers and the people of Uganda! 👉🏿 https://t.co/utwXAUaesh pic.twitter.com/vtftOgPQyq — WHO African Region (@WHOAFRO) January 11, 2023 At the same time, squashing the virus also has squashed the near-term prospects for a conventional clinical trial of three vaccine candidates that could prevent illness from the Sudan strain of the virus. WHO had originally planned to commence the randomized controlled trial last month in collaboration with Ugandan authorities. The trial was to be based on trials a convential demonstration of vaccine efficacy in a study group that would get the vaccine right away – as compared to a control group that would only get the vaccine after 21 days. See related story: Exclusive: Vaccine Trial Against Sudan Ebolavirus – With No Recent Infections in Uganda, What’s Plan B? Similar trials were undertaken in Guinea for vaccine candidates against the Zaire form of the virus during the 2014-2016 West African Ebola epidemic. The Merck vaccine candidate tested at the time, was eventually approved by United States regulatory authorities, after it helped bring an end to that tragic episode that killed over 11,000 people. A second vaccine, by Johnson & Johnson, was later tested and aprpoved by the European Medicines Agency in 2020. Is showing efficacy with animal models the best way forward? Microscopic image of an ebolavirus Health Policy Watch conversations in late December with vaccine experts inside and outside of WHO, as well as with two of the three manufacturers of the Sudan Ebolavirus vaccine candidates, underline that a new strategy for testing the vaccines will now be needed. And that is due to be discussed by WHO at Thursday’s meeting. “Historically the number of cases of the Sudan Ebolavirus has been very limited,” one expert interviewed by Health Policy Watch also observed. Small outbreaks of only a handful of cases would deeply challenge any attempt to obtain statistically significant results from a randomized controlled trial of even one vaccine candidate, let alone three. In the absence of any outbreak at all, experts have suggested that the most feasible pathway to regulatory approval might be throught the US Food and Drug Administration’s Animal Efficacy rule. The approach could involve the testing of vaccine efficacy, per se, on non-human primates, along with more extensive testing of the vaccine’s safety and ability to produce an immune response, in healthy human volunteers. The FDA’s animal efficacy rule is designed for just such situations, allowing initial regulatory approval of a vaccine for rare but deadly diseases based on animal model studies that replicate human disease, combined with evidence of safety and a strong immune response from clinical trials in healthy volunteers. Such a model was used by Bavarian Nordic to gain US Food and Drug Administration approval of its MVA-BN® vaccine in 2018 against smallpox, which was then available for a rollout this year on a compassionate use basis in response to the global outbreak of monkeypox, which WHO now recommends calling mpox. Once mpox became widespread, clinical trials of vaccine efficacy in humans also commenced. Developers of the vaccine candidates are quietly looking at such pathways to initial approval of Sudan ebolavirus vaccines. But it’s clear that the developers would also like the official, and proactive support of WHO for a new strategy, as the global health agency leading Africa’s Ebola response and the key partner of Uganda’s Ministry of Health as well as other countries on the continent in the Ebola battle. “One would have to decide if it would be possible to test the vaccines clinically, or go for plan B, and accept the animal rule, whereby the vaccine is approved on the basis of experimental work, with non-human primates along with very robust safety and immunogenicity trials,” said an independent clinical trial expert with knowledge of the trial who spoke with Health Policy Watch. Added another: “it would make a lot of sense to use the impetus of this outbreak, and the momentum that has been built, to do safety and immunogenicity trials, and then work in parallel on designing different Phase 3 trial [human] types that could be suitable for different types of outbreaks that might come in the future – trials of different intensity and so on, so that everything is ready to start the Phase 3 trials when the next outbreak comes.” Ensuring adequate stockpiles of vaccine candidates Swati Gupta, IAVI Ensuring adequate stockpiles of the vaccine candidates in the field is another compelling concern – and on that point there appears to be broad agreement within WHO and beyond. Such stockpiles exist for approved Ebola vaccines – but not for candidates that also could and should be deployed quickly among volunteers should another outbreak emerge. As the experience with the recent outbreak demonstrates, while the first Sudan ebolavirus vaccine candidates arrived in Kampala, Uganda in a record 79 days after the outbreak was first declared, that was still not fast enough – since by that time cases had dwindled, and most of the Ebola case contacts had already passed the 21-day virus incubation period without developing symptoms. “When there is no outbreak, we need to ensure that we have adequate funding and resources are allocated so that people can produce the stockpiles, and then have a discussion about where you’re going to keep them, and how you would utilize them if there was a need,” Swati Gupta, head of emerging infectious disease and scientific strategy at IAVI, a leading ebolavirus vaccine developer. “So we 100% support generating stockpiles and being prepared in advance.” The WHO consultation from 14:00-18:45 p.m. CET is open to participation with registration in advance. Registration link here: Image Credits: @WHOAFRO, @WHOAFRO, Brittanica © jaddingt/Shutterstock.com. Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Combat the infodemic in health information and support health policy reporting from the global South. Our growing network of journalists in Africa, Asia, Geneva and New York connect the dots between regional realities and the big global debates, with evidence-based, open access news and analysis. To make a personal or organisational contribution click here on PayPal.