From outbreak response to regional readiness: reimagining mRNA vaccine platforms for Ebola preparedness in East Africa

Introduction

Ebola outbreaks do not arrive as neat biological events. In East Africa, they move through health facilities, markets, burial practices, family networks, transport corridors and borderlands where people cross for work, trade and care. A single confirmed case in Kampala, Kasese, Gulu, Bunia or Goma can quickly become more than a local alarm. The virus tests laboratories, health worker protection, public trust, political coordination and the speed at which science reaches people who are already frightened.

Uganda’s recent experience shows both the danger and the opportunity. The country has faced repeated Sudan virus disease outbreaks, including the large 2022 outbreak (1) and the shorter 2025 event, while also building real capacity in surveillance, isolation, contact tracing and risk communication. WHO reported that the 2025 Sudan virus disease outbreak in Uganda was declared on 30 January 2025 and ended on 26 April 2025 after 14 total cases, including 12 confirmed cases, two probable cases and four deaths (2). Small does not mean simple. That outbreak still involved multiple districts, exposed health workers and contacts who had to be traced, monitored and supported.

The uncomfortable issue is that vaccine readiness is uneven across Ebola viruses. The success of rVSV-ZEBOV against Zaire ebolavirus is one of the major achievements of outbreak vaccinology. Ring vaccination in Guinea showed substantial protection, and expanded outbreak use helped make vaccination a practical part of Ebola response (3, 4). East Africa, however, cannot build its future around a Zaire ebolavirus tool alone. Sudan and Bundibugyo ebolaviruses remain central to regional risk, and the vaccine pipeline for them has been thinner, slower and more dependent on emergency improvisation.

This is where mRNA vaccine platforms deserve a more serious East African conversation. Not as a slogan, and not as a leftover argument from COVID-19, but as a platform that could be prepared in advance, adapted quickly and governed locally. Preclinical studies suggest that RNA or mRNA vaccines expressing Ebola or Sudan virus glycoproteins can generate protective immune responses in animal models (5–7). The harder questions are whether East Africa can build the surveillance, regulatory, manufacturing, trial and community systems needed to use such platforms when they matter most and, critically, whether the funding models that have underpinned African research capacity can sustain the kind of routine readiness that preparedness demands.

Why East Africa needs a platform mindset

A product mindset waits for a specific vaccine. A platform mindset prepares the system that can update, test, produce and deliver candidates as threats change. For East Africa, that distinction is practical rather than theoretical. Ebola risk is species-specific, geographically uneven and socially fast-moving. A district can move from one suspicious death to hundreds of monitored contacts in a few days. If the scientific system starts only after confirmation, it is already late.

The 2025 Uganda response gives a concrete example. WHO and partners worked with Ugandan investigators, regulators and international filovirus experts so that candidate vaccines and treatments could be accessed once Sudan virus disease was detected (8). A clinical efficacy trial for a vaccine against Ebola disease caused by Sudan virus was launched during the emergency (9). Adepoju (10) and Anderer (11) described this as a landmark moment for Sudan virus disease vaccine evaluation. That speed should be celebrated. It should also make the region restless. If so much had to be assembled under pressure, the next task is to make readiness less heroic and more ordinary.

This imperative aligns with the 100 Days Mission framework and the Coalition for Epidemic Preparedness Innovations (CEPI) platform technology approach, both of which emphasize the need to move from viral detection to vaccine deployment within shorter timeframes (12). CEPI has established platform technologies as a strategic priority for epidemic response, particularly evident in their response to recent Ebola disease outbreaks caused by Bundibugyo virus. A platform mindset in East Africa would embed these principles directly into regional institutional structures, ensuring that the region is not dependent on emergency mobilization but rather operates within a pre-established architecture of genomic capacity, regulatory frameworks and manufacturing readiness.

East Africa also has the geography of shared risk. The Democratic Republic of the Congo, Uganda, Rwanda, South Sudan, Tanzania and Kenya are tied together by formal and informal movement. People travel before alerts are issued, cross borders before laboratory results return and seek care where they believe they will be helped. In that setting, cross-border preparedness is a vaccine issue as much as a surveillance issue. A vaccine kept in a distant freezer is not readiness if it cannot be approved, transported, explained, administered and monitored where exposure is occurring.

The scientific case for mRNA Ebola vaccine readiness

mRNA vaccines deliver genetic instructions that allow host cells to produce a target antigen, usually through lipid nanoparticle delivery. The platform has features that matter for outbreak-prone pathogens: rapid design after sequence availability, manufacturing processes that can be standardized across targets and the option of testing updated constructs without rebuilding the entire production chain (13, 14). For Ebola disease, the glycoprotein remains the obvious starting point because it mediates viral entry and has been the central antigen for several vaccine approaches.

The evidence base is early, but it is no longer empty. Meyer et al. (5) reported that lipid nanoparticle-formulated modified mRNA vaccines based on Ebola virus glycoprotein induced Ebola-specific IgG and neutralizing antibody responses and protected guinea pigs after challenge. O'Donnell et al. (6) extended the RNA platform logic to Sudan virus by showing single-dose replicon RNA protection in female guinea pigs. Stromberg et al. (7) reported that an mRNA vaccine expressing Ebola virus glycoprotein induced high neutralizing antibody titers and protected mice against lethal challenge. These are not field efficacy data, and they should not be sold as such. Still, they justify serious platform development, especially for viral species where licensed vaccines remain unavailable.

Other vaccine platforms make the same point from a different angle. Vesicular stomatitis virus-based Sudan virus vaccines have protected macaques in challenge studies (15), and bivalent ChAdOx1 Ebola and Sudan virus vaccination has shown early clinical safety and immunogenicity in adults (16). The field is clearly moving beyond Zaire-only preparedness. mRNA candidates should therefore be judged alongside these approaches on durability, T cell responses, reactogenicity, tropical stability, dosing schedule, performance in previously exposed populations and feasibility during ring vaccination. Excitement is useful only if it survives field reality.

From vaccine pipeline to regional preparedness ecosystem

A serious argument for mRNA Ebola preparedness cannot stop at biotechnology. The region needs an ecosystem. Genomic surveillance should identify the species and sequence relevant targets quickly. Regional laboratories should handle sequencing data, immunological assays and quality control. Regulators should maintain pre-reviewed emergency pathways that preserve rigour without wasting time. Trial sites need trained staff, community networks, adverse event monitoring and data systems before an outbreak begins.

Parts of this architecture already exist. Uganda has strong research institutions and considerable outbreak experience. The WHO mRNA technology transfer hub in South Africa was established to strengthen mRNA vaccine production capacity on the continent and to support African manufacturing self-determination beyond COVID-19 (17). This initiative has significant implications for East Africa: rather than importing finished vaccine products, the region could develop capacity in antigen design, batch release, and quality assurance systems through partnership with the hub. However, establishing functional mRNA manufacturing capacity carries substantial infrastructure and regulatory challenges. Recent experience in South Africa demonstrates that facilities require significant capital investment, sustained technical expertise, and rigorous good manufacturing practice certification protocols. East Africa must engage with these realities honestly, considering whether regional facilities should focus initially on fill-and-finish operations, quality control, and temperature-stable formulation work rather than attempting full synthesis capacity.

Africa CDC’s Partnerships for African Vaccine Manufacturing places vaccine production within a wider continental health security agenda (18). Beyond these existing platforms, regulatory harmonization emerges as a critical enabling function. Currently, fragmented national regulatory pathways create substantial burdens for manufacturers submitting product dossiers across multiple East African jurisdictions. The African Medicines Agency (AMA) and Africa CDC are positioned to accelerate preparedness by developing convergent regulatory standards and pre-approved trial protocols for investigational mRNA vaccines. This harmonization would reduce both the time and cost for bringing candidates into outbreak response trials.

Additionally, the Global Coalition for Local and Regional Production, Innovation and Equitable Access (launched under Brazil’s G20 Presidency) represents an emerging framework for regional manufacturing ecosystems. Though currently focused on dengue, this initiative has signaled openness to platform technologies including mRNA approaches for a range of diseases. East Africa should engage actively in coalition discussions to position regional capacity-building for potential future investment.

Preparedness would mean prepositioned trial protocols, harmonized ethics templates, regional agreements for sample sharing, standardized assays for Ebola glycoprotein responses, mapped cold chain capacity and procurement plans before panic begins. It would also mean speaking honestly with communities about what an investigational vaccine is, what mRNA is and what remains unknown. People can live with uncertainty when they are treated with respect. They rarely accept being surprised by it.

Community trust is part of the platform

Ebola vaccination is not simply an injection. It is a social act carried out during fear. Communities may be grieving, angry or suspicious. Health workers may be exhausted. Rumors may move faster than contact tracing teams. The term mRNA may also bring back memories of COVID-19 disputes, political messaging and online misinformation. If mRNA Ebola preparedness is built only in laboratories, it may fail at the clinic gate, the village meeting or the burial negotiation.

Trust has to be prepared before the emergency. Survivors, religious leaders, local journalists, market leaders, ambulance teams, nurses, burial teams and community health workers should be part of the conversation from the start. They need to understand why a Sudan virus outbreak may require a different vaccine from a Zaire virus outbreak. They also need to know why trial participation can be ethical during an emergency and why safety monitoring continues after vaccination. This social layer is not a soft add-on. It is part of the platform.

Concrete solutions for community engagement should be drawn from proven frameworks in related disease areas. HIV and tuberculosis community mobilization efforts across East Africa have established credible models for sustained trust-building and meaningful participation. The IAVI action plan on accelerating broadly neutralizing antibodies for peripartum and postnatal HIV prophylaxis provides actionable examples of how communities can be embedded in product development from the design phase through post-trial access (19). These models demonstrate how survivor-led advisory groups, community-based monitoring networks, and feedback loops between trial participants and investigators can shape both trial design and outcomes.

Religious institutions deserve particular attention in this regard. Faith communities across East Africa command deep trust and wide reach. During the 2014–2016 West Africa Ebola epidemic, religious leaders were pivotal in shaping community responses to safe burial practices, quarantine compliance and messaging about rumors (20). Their involvement in mRNA vaccine preparedness could be equally decisive: they can serve as credible communicators, community mobilisers and, in some contexts, sources of moral legitimacy for trial participation. At the same time, religious networks can amplify misinformation with the same efficiency with which they transmit reassurance. Engaging faith leaders early before outbreaks, not during them is therefore a structural requirement, not an optional courtesy.

The 2025 Uganda trial demonstrates that speed can be ethically powerful when built on preparation. Candidate vaccines did not enter a vacuum; they entered a response shaped by Ugandan institutions, WHO coordination and earlier planning (8, 9). Future mRNA trials should extend this model by ensuring that African scientists lead protocol design, local communities understand the terms of participation and successful products remain accessible after evidence is generated. Importantly, community trust is not a final stage in the preparedness pathway but should be embedded throughout each phase: in genomic surveillance communication, in antigen selection discussions, in manufacturing transparency, in trial site selection, and in post-trial access negotiations. This integrated approach ensures that community voices shape preparedness architecture from inception rather than serving as an afterthought.

Manufacturing, cold chain and delivery

mRNA readiness will mean little if the vaccine cannot leave the capital. Ebola outbreaks may occur in rural districts, conflict-affected zones, mining corridors, crowded urban settlements or border communities where electricity, roads and internet coverage are unreliable. Some mRNA products have demanding cold chain requirements, although formulation and stability work continues to improve (13). The field question is blunt: can the vaccine reach contacts, health workers and high-risk communities fast enough to matter?

Delivery models should match outbreak epidemiology. Ring vaccination remains attractive because it targets contacts and contacts of contacts around confirmed cases; the Ebola ça Suffit trial made that strategy central to Ebola vaccine evidence (4). Health worker vaccination may be needed early because nurses, laboratory staff, ambulance teams and cleaners can become both victims and amplifiers if infection prevention fails. In Kampala, a ring may look different from a ring around a rural household cluster. Preparedness must allow that flexibility.

Supply chain fragility presents a structural obstacle that the mRNA Ebola preparedness agenda must confront honestly. African laboratories and health facilities have long depended on imported reagents, cold chain equipment, consumables and specialized components for molecular science. Disruptions whether caused by global procurement bottlenecks, shipping delays, foreign exchange shortfalls or sudden export restrictions can halt testing, undermine biosafety and erode the institutional confidence that outbreak response demands. The COVID-19 pandemic exposed this dependence acutely: diagnostic reagents became scarce precisely when demand was highest, and mRNA manufacturing inputs faced competition from high-income country buyers with greater purchasing power (21). An mRNA Ebola preparedness program that does not include regional strategies for reagent stockpiling, local production of critical consumables and diversified procurement relationships will be vulnerable to the same failures.

Manufacturing is equally political. East Africa does not need every country to build a full mRNA plant. It does need meaningful participation in antigen selection, batch release, quality systems, pharmacovigilance, trial leadership, fill-and-finish capacity where feasible and data ownership. Otherwise, mRNA preparedness risks becoming another form of dependence with better branding.

Table 1 outlines the key domains required for integrating mRNA vaccine platforms into a sustainable Ebola preparedness ecosystem in East Africa, highlighting their relevance to vaccine readiness and associated public health implications.

Table 1. A regional framework for mRNA-enabled Ebola preparedness in East Africa.

The framework treats mRNA vaccine development as a regional preparedness system, not as a single emergency commodity.

Funding, sustainability and the structural realities of African science

Any serious proposal for mRNA Ebola preparedness in East Africa must reckon with what may be its most formidable obstacle: the way science is funded on the African continent. Readiness is not a project that can be activated, completed and closed. It is a continuous state a maintained condition of institutional memory, trained personnel, functional infrastructure and regularly rehearsed protocols. That kind of continuity is extremely difficult to sustain through the dominant model of African research financing, which has long depended on competitive international grants won institution by institution, discipline by discipline and often year by year.

Ugandan research institutions have built genuine capacity over decades, but much of that capacity sits on a fragile financial foundation (22). When a grant cycle ends, trained laboratory scientists may leave for better-paid positions, data systems may go unmaintained and community engagement networks may go dormant. The competence that made a trial site functional during one outbreak may not be present in the same form when the next begins. This is not a criticism of the institutions or the individuals who built them. It is a structural description of what happens when readiness is financed as a series of projects rather than as a public good.

The recent and severe contraction of international research funding has sharpened this concern considerably. Cuts to United States foreign assistance and the rollback of major global health funding streams have affected African research institutions, clinical trial networks, surveillance systems and community health programs simultaneously (23). Institutions that had achieved meaningful capacity in genomic surveillance, laboratory quality management or trial operations are now facing staff reductions, supply shortfalls and uncertain program futures. An mRNA Ebola preparedness initiative that does not engage with this funding landscape is not a serious proposal it is a technical wish list.

The case for a different model is not simply moral. It is epidemiological. Ebola preparedness has a negative relationship with financial discontinuity: every gap in surveillance, every hiatus in laboratory maintenance and every period in which trained staff are unretained is a gap in which an outbreak can move from a single case to a regional emergency before detection. The cost of reactive response in 2014 was estimated in the tens of billions of dollars; the cost of sustained preparedness is a fraction of that (24). African governments and their international partners have repeated this arithmetic in policy documents for a decade. The gap between the stated case and actual budget allocation remains large.

Sustainability also depends critically on establishing a credible business case for mRNA vaccine manufacturing. Long-term demand cannot rely solely on pandemic preparedness; instead, mRNA platforms must serve as health innovation tools across a broader range of endemic and non-communicable diseases. This diversification would provide manufacturers with continuous year-round production, diversified product portfolios and stabilized revenue streams conditions essential for justifying capital investment and retaining specialized workforce capacity. East African countries should conduct health needs assessments identifying diseases beyond Ebola where mRNA platforms could address critical medical needs, including improved malaria vaccines, tuberculosis boosters, or maternal immunization strategies. This market-oriented approach strengthens the financial case by demonstrating that regional manufacturing capacity serves multiple public health goals, not just crisis response, and generates the sustained demand necessary for long-term economic viability.

What would a more sustainable financing architecture look like? Several elements are worth identifying. First, national health budgets in East African countries should treat Ebola preparedness as a recurrent line item rather than a project expense. This requires political will and fiscal space that not all governments currently have, but it also requires a shift in how preparedness is defined in budget negotiations—as an investment that reduces future liability rather than a discretionary expenditure in competition with other health priorities.

Second, inter-governmental mechanisms in the region offer underused platforms for shared preparedness financing. The East African Community has a formal framework for health cooperation, and the African Union’s Africa CDC has demonstrated that continental coordination can accelerate outbreak response. However, the translation of these frameworks into pre-committed preparedness budgets rather than pledging conferences convened after fear has already spread has been limited. A regional mRNA Ebola preparedness fund, modelled on the pandemic preparedness financing mechanisms proposed but only partially implemented after COVID-19, could pool contributions and reduce the dependence of individual countries on bilateral grant flows.

Third, African-led investment in science infrastructure reagent manufacturing, laboratory consumables, cold chain equipment and training would reduce the supply chain fragility that characterizes the current model. This is not simply a matter of scientific self-sufficiency as an abstract goal. It is a matter of functional independence during outbreaks when import-dependent systems are most vulnerable. Initiatives such as the African Continental Free Trade Area could, if health supply chains are explicitly included in implementation frameworks, begin to shift the balance.

Finally, the scientific community has a role in making the public case for sustained investment. Peer-reviewed publications from African researchers, presented in journals accessible to policymakers and published in ways that reach African audiences, are part of an advocacy infrastructure that has too rarely been mobilized around research funding itself (25). Funders should be challenged to move beyond project grants toward institutional development support. African governments should be challenged to raise domestic research investment as a share of GDP. The case for both is strengthened, not weakened, by the evidence of what was achieved during the 2022 and 2025 Uganda outbreaks when prior investment was present.

The figure presents a regional framework for integrating mRNA vaccine platforms into Ebola preparedness in East Africa. The pathway progresses from genomic surveillance and pathogen sequencing to mRNA vaccine design, preclinical evaluation, regulatory and trial readiness, manufacturing and supply-chain preparation, and targeted outbreak vaccination, followed by post-deployment monitoring and adaptation. Central coordination by regional institutions, governments, academia, and communities supports all stages. Cross-cutting enablers including workforce development, community engagement, equity, sustainable financing, regional partnerships, and One Health integration underpin the system, aiming to strengthen outbreak readiness, vaccine equity, and regional health security (Figure 1).

Research priorities

The next research agenda should be deliberately practical. Immunology studies should compare mRNA constructs for Sudan, Bundibugyo and Zaire ebolavirus glycoproteins using standardized assays that African laboratories can run or interpret. Neutralizing antibodies matter, but they are not the whole story. Durability, Fc-mediated functions, mucosal responses and cellular immunity should also be assessed, especially if dose-sparing strategies are considered.

Field-oriented trials should test delivery models, not only vaccine products. A two-dose mRNA regimen may be scientifically acceptable but operationally awkward during a fast outbreak if contacts are mobile. A thermostable formulation could matter as much as a modest gain in antibody titer if it changes what is possible in a rural district. Trial designs should therefore measure feasibility, follow-up completion, cold chain excursions, community acceptance and speed from case confirmation to vaccination.

Social science should be built into vaccine research from the start. What do health workers in Uganda think when they hear the phrase mRNA Ebola vaccine? How do border communities distinguish between a licensed vaccine, an investigational vaccine and an emergency use product? Which messengers are trusted when fear is high, and how does the role of religious authority intersect with public health communication in different community contexts? These questions may sound plain, but they decide whether a technically strong vaccine becomes a public health tool or a rejected intervention.

Workforce training and capacity development emerge as critical research gaps that are often overlooked in technology-focused agendas. East Africa must strengthen its pipeline of scientists, biomanufacturers and technicians specifically trained in mRNA platform technologies and cold-chain logistics. This requires targeted investment in educational partnerships, internship program within manufacturing facilities, and support for young African scientists pursuing specialized training in mRNA synthesis, formulation and quality control. Research priorities should include studies measuring the effectiveness of different workforce development models, tracking retention of trained personnel, and identifying factors that enable talented African scientists to remain engaged in regional research institutions rather than migrating to high-income countries.

Regional frameworks such as the G20’s Science and Innovation for Health and Economic Growth initiative offer relevant policy guidance for structuring these priorities. East African governments should draw on these models when prioritizing science within competing political agendas, using evidence of vaccine platform benefits to strengthen budget arguments and inter-governmental coordination.

Health economics and funding research should sit alongside immunology and social science as explicit research priorities. Studies that estimate the long-term cost of preparedness versus reactive response, that model the institutional losses associated with funding gaps and that describe the conditions under which African governments and regional bodies could sustain preparedness investment would generate evidence relevant to policymakers in ways that immunogenicity data alone cannot.

Discussion

The case for mRNA Ebola preparedness in East Africa is strongest when it is modest and concrete. mRNA platforms may shorten the pathway from sequence to candidate vaccine and allow rapid updating for species-specific threats. They will not replace case detection, isolation, infection prevention and control, safe burial practices, contact tracing, community engagement or clinical care. A vaccine platform is only one part of outbreak control, even when it is sophisticated.

The deeper argument is readiness. East Africa has shown that emergency vaccine trials can be activated quickly when prior planning exists (9, 10). The region should now ask what it would take to make such speed normal. That requires investment in people as much as platforms: trial nurses, laboratory scientists, data managers, regulators, logisticians, community engagement teams and manufacturing specialists. It also requires political seriousness. Preparedness budgets are easy to cut when there is no outbreak on the evening news.

There are risks. mRNA Ebola vaccines are not yet proven field tools. Preclinical protection in guinea pigs or mice does not guarantee effectiveness in humans exposed during an outbreak (5–7). Reactogenicity, dosing schedules, durability and cold chain demands could limit use. There is also a fairness risk. If mRNA platforms are developed mainly through external ownership, with African sites used only when outbreaks occur, the technology may repeat old inequities. That would be a poor version of innovation.

The funding and sustainability challenge discussed above adds a further layer of risk that is not often named in scientific papers: the possibility that preparedness architecture, even when well designed, collapses between outbreaks because the financing that maintains it is discontinuous, politically vulnerable or tied to international priorities that shift faster than regional epidemiology changes. The 2025 Uganda trial was a landmark, but it succeeded in part because of investments made years earlier in laboratory infrastructure, regulatory capacity and community-engaged research networks. Those investments were themselves dependent on sustained international funding. As that funding environment becomes less reliable, the region faces a choice: develop more durable domestic and inter-governmental financing, or accept that the next outbreak may find the readiness architecture in a worse state than the last one.

Still, the opportunity is real. Ebola preparedness has often been framed as a race against time. mRNA platforms can help with time, but only if the region prepares the track before the race begins. That preparation includes not only genomic sequencing capacity and cold chain logistics but also financing structures, supply chain resilience and the political commitment to treat readiness as a permanent feature of the regional health system rather than a crisis supplement. That is the shift this Perspective argues for: from admiring new vaccine technology to asking how East Africa can govern, test, produce and deliver it on its own terms and on a sustainable financial basis.

Conclusion

East Africa should reimagine mRNA vaccine platforms as part of Ebola preparedness infrastructure rather than emergency commodities that arrive after fear has already spread. The region faces a species-diverse Ebola threat, with Sudan and Bundibugyo ebolaviruses especially important because licensed vaccine options are limited or absent (26). mRNA platforms could add speed, adaptability and scientific flexibility, but only if they are embedded in genomic surveillance, regulatory readiness, ethical trial systems, community trust, cold chain planning and African manufacturing capacity. That embedding requires sustained financing not the episodic grant cycles on which much of African science has historically depended, but predictable, domestically anchored and regionally coordinated investment in preparedness as a public good. The recent contraction of international research funding makes this shift more urgent, not less. The next Ebola outbreak should not find the region beginning again. It should find a prepared ecosystem already capable of moving from viral sequence to local readiness with speed, fairness and scientific confidence and the financial architecture to sustain that capability between outbreaks.

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Footnotes

Edited by: Harapan Harapan, Syiah Kuala University, Indonesia

Reviewed by: Faith H. A. Osier, KEMRI Wellcome Trust Research Programme, Kenya

Sanjana Mukherjee, Georgetown University, United States