WHO's Ongoing Ebola Vaccination Efforts in the DRC
For roughly 10 months, the Democratic Republic of the Congo (DRC) has been battling the second largest Ebola epidemic in recorded history. As of May 29, there were 1,954 total reported Ebola cases, including 1,312 deaths. Instability in the region and violence specifically targeting healthcare workers/facilities have exacerbated the severity of the outbreak and impeded response efforts. These underlying contextual challenges have created an extremely volatile landscape, and increasing incidence raises concerns that the epidemic may continue to grow and spread to new areas.
Investigational vaccines are one novel tool that have become available since the 2013-16 West Africa Ebola epidemic, at least on a scale that can be employed during a response. These vaccines have shown promise in providing safe and effective protection from Ebola Virus infection, but all candidates are currently still in experimental phases. Outbreak Thursday previously detailed these new vaccines and their implications for response efforts. This week’s post will provide an updated look at the status of the investigational vaccines and explore the role of vaccination during this epidemic, the recent decision by the WHO to alter its vaccination strategy, and the reasons why some officials in the DRC are hesitant to comply with certain changes.
The WHO Vaccine Strategy
Initially, the WHO vaccination strategy aimed to inoculate 2 high-risk groups within the DRC: frontline healthcare workers and primary and secondary contacts (ie, “contacts of contacts”) of known Ebola cases. Thus far, vaccination of the contacts has been conducted primarily through an ongoing ring vaccination effort. Healthcare workers and other responders build a list of at-risk individuals based on social connections to known cases derived through contact tracing. These efforts have proven challenging during the the DRC outbreak due to security concerns and broad mistrust in the government and response.
In mid-April, the WHO released preliminary data for ongoing vaccination efforts with the Merck vaccine. During the study period, there were 951 identified Ebola cases in the DRC. Among these cases, responders were able to establish complete contact tracing for 679 cases and identify partial contact networks for another 97. The remaining 175 cases were not able to undergo further investigation due to security concerns or lack of patient consent. These vaccination efforts led to 93,965 vaccinations among identified contacts. Only 71 vaccinated individuals were later determined to be infected with Ebola—and only 15 of these were diagnosed more than 10 days after vaccination—demonstrating the vaccine’s efficacy.
When these preliminary data were released, the authors seemed optimistic about the WHO vaccine strategy. Ring vaccination had managed to largely prevent additional cases within contact groups, and there seemed to be sufficient vaccine supply to sustain continued ring vaccination activities. Unfortunately, the Ebola outbreak took a turn for the worse in the following month, fueled by waves of unrest in affected areas. In response to the uptick of cases in April 2019, the WHO revised its vaccination strategy based on a set of recommendations developed by the Strategic Advisory Group of Experts on Immunization (SAGE). The recommendations included a 5-part plan to strengthen their vaccination effort in light of the increasing Ebola incidence. These components revolved around expanding the target population and providing new techniques to mitigate operational challenges. The strategy expanded the scope of ring vaccination activities to include tertiary contacts, which would greatly increase vaccination efforts, including the supply necessary to cover the additional contacts.
As a way to account for this surge in vaccination activity, the WHO strategy decided to bring in Johnson & Johnson’s (J&J’s) investigational vaccine as a secondary option for lower-risk groups. This decision also aligned with a previous recommendation in April from SAGE, which strongly urged the evaluation of additional Ebola vaccine candidates. While incorporating this vaccine in outbreak response could help address the increased demand for vaccine for the updated strategy, this will be the first time the vaccine has been used in the outbreak, and its inclusion has received a mixed reception from certain groups involved in the Ebola response.
DRC’s Two Ebola Vaccines
Merck’s rVSV-ZEBOV was the sole Ebola vaccine used during the first 10 months of the outbreak. In 2015, the WHO determined that the vaccine was suitable for use in outbreak responses, and the vaccine received a “Breakthrough Therapy Designation” from the US Food and Drug Administration (FDA) in 2016. These approvals helped solidify the Merck vaccine as a primary candidate in future Ebola outbreaks, and the WHO developed a vaccine strategy under a “compassionate use protocol.”
In the year following the start of vaccination efforts with the Merck vaccine, the vaccine has reinforced its reputation as both safe and protective. The preliminary data published in April indicated the vaccine demonstrated 97.5% efficacy. Additionally, the report noted that most of the vaccinated individuals who were infected were diagnosed within 10 days of receiving the vaccine, a period during which their body may still have been building immunity. Merck has continued to pursue the process of full commercialization for their Ebola vaccine, but has yet to reach full approval.
Until now, the WHO Ebola vaccination effort in the DRC has exclusively used the Merck vaccine, but the new revisions to the WHO vaccine strategy indicate that the J&J vaccine, MVA-BN (Ad26.ZEBOV/MVA-BN), will soon join the fight. The J&J vaccine has also shown promise in early clinical trials, and its use in the DRC would also be under a compassionate use protocol.
DRC’s Call for Merck, Not J&J, Vaccine
Although the WHO’s adapted vaccination strategy includes a number of important changes, the decision to add the J&J vaccine to the response efforts attracted media and expert attention. SAGE’s intended for the J&J vaccine to be an alternative option for lower-risk individuals. The recommendation specifically cites a WHO review from April that addressed the issue of adding new candidate vaccines to the Ebola response. In this review, the J&J vaccine scored a 41 out of a possible 44 points in categories like vaccine stability, safety, and availability.
Based on these review results, it is not overly surprising that the SAGE recommendation proposed the introduction of the J&J vaccine. However, despite this high level of institutional confidence, DRC officials expressed resistance to introducing the new vaccine, calling for an increased effort to expand the use of the Merck vaccine rather than introduce the new J&J product. These officials noted that adding a second vaccine could pose operational and communication challenges.
The two vaccines share a number of similarities, but there are a number of key differences that may impact the logistics of their use in the outbreak. Both aim to protect the Zaire strain of Ebola, target individuals over the age of 18, and require cold chain for transportation and storage. The main difference in their indication. The Merck vaccine requires only a single dose, and is indicated as a reactive vaccine. On the other hand, the J&J vaccine requires 2 doses, administered almost 60 days apart, and it is indicated only for those who have not yet been exposed. These key differences could create a number of logistical and communication challenges for health workers in the DRC, which could further complicate response operations.
Using the J&J vaccine as a preventative vaccine in lower-risk groups makes sense, considering that the vaccine requires a booster dose 60 days after the original shot. Additionally, this would allow available supply of the Merck vaccine to be reserved for higher-risk individuals who may have already been exposed to the virus. This combined approach allows responders to continue ring vaccination efforts, while bolstering the immunity of the broader community. In principle, this would be a more robust response to the disease outbreak; however, the instability in the region could inhibit the follow-up process necessary to administer booster. From a communication perspective, the use of two separate vaccines increases the importance of clear messaging and provide additional opportunity for confusion or uncertainty amongst community members, a critical challenge among communities with deep-seeded trust issues with the government. There is primary evidence that widespread misinformation has already led to increased institutional distrust amongst community members, and there is concern that the introduction of a new vaccine that requires different messaging may further alienate at-risk communities.
A two-dose vaccine designed to confer long-term immunity in advance of an outbreak may not be ideal for outbreak response operations, but the the use of this vaccine in lower-risk individuals during the DRC outbreak could serve two purposes: (1) expand the pool of protected individuals around known cases and (2) provide critical data for use in evaluating the J&J vaccine’s safety and efficacy. Vaccination with the single-dose Merck vaccine will continue be the primary component of the vaccination efforts, and the introduction of the J&J vaccine enables the WHO to expand the vaccination efforts without impacting the primary ring vaccination strategy. Assuming the WHO moves forward with these recommendations, we can hope that this robust vaccination strategy will reduce the spread of the outbreak and bring an end to this outbreak.
Photo courtesy of Alaine Kathryn Knipes via CDC
Outbreak Observatory aims to collect information on challenges and solutions associated with outbreak response and share it broadly to allow others to learn from these experiences in order to improve global outbreak response capabilities.