The declaration that the mpox outbreak in the Democratic Republic of Congo is over marks more than the end of a two-year emergency. It highlights a quiet revolution in vaccine development and deployment. From repurposed smallpox shots to single-dose innovations and mRNA candidates now in trials, mpox vaccines have evolved faster than many expected. In Africa, where the burden was heaviest, local leadership, targeted vaccination and community trust proved decisive. Yet as Africa CDC celebrates this win, experts warn that sustained investment is needed to stay ahead of the next outbreak.
When mpox clade Ib exploded in eastern DRC in late 2023, the continent faced a familiar threat: a virus with roots in smallpox vaccines, but almost no modern tools readily available in Africa. Two years and more than 2,200 suspected deaths later, the outbreak is officially over. The turnaround did not happen by chance. It came through a combination of repurposed vaccines, rapid African-led deployment and the first glimpses of next-generation candidates that could change the game for future outbreaks.
The two main vaccines that helped turn the tide were already known. MVA-BN (marketed as JYNNEOS or IMVANEX by Bavarian Nordic) is a non-replicating modified vaccinia Ankara vaccine. It received WHO prequalification in 2024 and became the first vaccine formally approved for mpox. LC16m8, a single-dose replicating vaccine from Japan, was deployed in the DRC through bilateral donations and is now being studied for real-world effectiveness in African children and adults.
How the Approved Vaccines Made the Difference
Africa CDC and the DRC Ministry of Health coordinated the delivery of hundreds of thousands of MVA-BN doses across 16 countries, with the DRC receiving the lion’s share. Dose-sparing strategies – including intradermal fractional dosing – stretched limited supplies further. Real-world data showed strong protection: two doses of MVA-BN offered 82% effectiveness, while even a single dose reduced severity. LC16m8’s single-dose regimen proved especially useful in hard-to-reach areas.
Community health workers played a starring role. In Equateur Province and other hotspots, trusted local teams explained the vaccine in local languages, addressed fears and ensured high uptake. Vaccine acceptance reached 61% overall, higher among health workers and people in endemic zones. That trust, built through consistent engagement, was as important as the shots themselves.
Next-Generation Candidates: Single-Dose and mRNA Hope
While the current vaccines helped end the emergency, developers are already racing toward better options. At the World Vaccine Congress in April 2026, GeoVax presented impressive preclinical data on its MVA-X candidate – a modified vaccinia Ankara vaccine enhanced with an immunomodulatory peptide. In a lethal orthopoxvirus challenge model, a single dose of MVA-X achieved complete protection comparable to the standard two-dose MVA regimen. Protection lasted at least 150 days, with strong T-cell responses and minimal disease severity.
GeoVax plans to start a pivotal Phase 3 immune-bridging study in the second half of 2026, aiming to expand global supply and address the two-dose limitation of current MVA-BN vaccines. The company says the platform could also support biodefense and public-health preparedness.
On the mRNA front, Moderna’s mRNA-1769 and BioNTech’s BNT166 candidates are in Phase 1/2 trials. These next-generation shots aim to elicit stronger, longer-lasting immunity with fewer side effects. Early data suggest they could overcome some of the limitations of traditional orthopoxvirus-based vaccines, particularly in immunocompromised populations.
Lessons from DRC: African Ownership Works
The DRC response was not a top-down international rescue. It was African-led. The Africa CDC mobilised over US$1 billion, expanded laboratory capacity, delivered millions of vaccine doses and coordinated with partners without ceding control. The result: cases dropped sharply, the emergency was lifted in January 2026 for the continent and the DRC followed in April.
This success stands in contrast to earlier global mpox waves in 2022–2024, when high-income countries received the bulk of vaccines while Africa waited. The 2023–2026 outbreak showed that when African institutions lead and partners support equitably, results follow.
Challenges That Remain
Vaccine equity is still an issue. Supply was limited throughout the outbreak, forcing dose-sparing and prioritisation. Funding gaps – including shifts in external support like PEPFAR – continue to threaten long-term surveillance and laboratory capacity. Immunity from current vaccines may wane after two years, according to data presented at CROI 2026, meaning boosters or better vaccines will be needed for sustained protection.
Manufacturing on the continent remains limited. Most doses still come from Europe, Japan or the United States. African leaders are pushing for local production to reduce dependence and speed up future responses.
Relevance for South Africa and the Continent
South Africa recorded no sustained local transmission during the outbreak, thanks to strong surveillance at ports and borders. But the DRC experience offers direct lessons. Cross-border travel and trade mean vigilance must continue. More importantly, the mpox response proved that community engagement and rapid deployment work – tools that could accelerate rollout of other innovations, such as the new six-monthly injectable HIV prevention jab currently being piloted in South Africa.
For the broader continent, the end of the DRC emergency is a sovereignty win. It shows that African public-health systems can deliver when properly resourced. The challenge now is to maintain that momentum: invest in local vaccine manufacturing, strengthen regional surveillance networks and ensure the next generation of mpox vaccines – single-dose, mRNA or multi-subunit – reaches those who need them first.
The Road Ahead
Mpox vaccine development has come a long way since the 2022 global emergency. What began as repurposed smallpox shots has evolved into a pipeline of next-generation candidates that could offer single-dose protection, broader immunity and easier deployment in low-resource settings. The DRC’s victory proves these tools work when paired with African leadership.
Yet the virus has not disappeared. Low-level circulation continues, and new clades or zoonotic spillovers remain possible. The real test will be whether the world – and Africa in particular – sustains the investment and political will now that the emergency is over. If it does, the next outbreak could be shorter, milder and far less deadly.
For now, the people of the DRC and the teams who fought this outbreak for two long years deserve to celebrate. Their success is not just a national story – it is a blueprint for how Africa can lead the next chapter in global health security.