Hantaviruses have been killing people for a long time. For most of that time, no one knew what was causing the deaths. Then came a particularly large outbreak in a place the entire world was watching.
During the Korean War in the early 1950s, . They developed high fever, their kidneys began to fail, and many had serious bleeding. By the time the armistice was signed, more than 3,000 United Nations troops had become sick, and at first the death rate was reported at about 15%. American military doctors called it “Korean hemorrhagic fever.” They were sure some kind of virus was behind it. They just could not find it.
The story of the vaccine against the virus that caused that outbreak starts with one scientist, a field mouse, and a river.
Ho Wang Lee and the Hantaan River
Professor Ho Wang Lee was . He spent years trying to find the cause of Korean hemorrhagic fever. In 1976, his team carried out a careful trapping project in a rural area north of Seoul. In the lungs of a small striped field mouse (), they finally found a viral antigen (a protein fragment from the virus) that matched what they were looking for. They confirmed it by showing that this antigen reacted with blood samples from people who were recovering from the disease.
Lee named the virus Hantaan, after the Hantaan (or ) River that runs through the region where his team caught the mice. Scientists around the world had been searching for this virus since the 1950s, so the discovery was a major moment for the field. Several members of Lee’s team became infected while working with the wild rodents, likely from breathing in tiny particles from the animals or their droppings.
Once the virus was identified, Lee quickly moved on to building a test to detect it and then to developing a vaccine. He was thinking about the whole path from discovery to prevention. By 1985, working with Green Cross Corporation (later GC Biopharma), he had shown that passing the virus through the brains of newborn mice made it weaker and safer to handle. (The same procedure Louis Pasteur used with the rabies virus and rabbits.) He then killed the virus with formalin, following World Health Organization standards for inactivated vaccines. . That December, South Korean media announced that the country had developed the world’s first vaccine against hemorrhagic fever.
In 1990, the Korean Ministry of Food and Drug Safety gave the vaccine conditional approval, meaning it could be used while more clinical trials were still underway. It was sold under the name ™. Lee had done something unique in modern medicine: he discovered a virus, created a lab test for it, and helped produce a vaccine against it, all for the same disease.
Hantavax: What It Does and What It Doesn’t
Hantavax works by helping the body make neutralizing antibodies against the Hantaan virus, the main cause of hemorrhagic fever with renal syndrome (HFRS) in parts of Asia. The dosing schedule has changed over time. It began with two doses a month apart, then a booster a year later. After a regulatory review in 2018, South Korea added a fourth dose. By then, tens of millions of doses had been given, mostly to soldiers, farmers, and other people who work in rural areas.
The big question has always been how well it protects. . But the estimates were not precise enough to rule out chance, so the results were uncertain. A field trial in parts of Yugoslavia in the late 1990s looked better: among about 1,900 vaccinated people, there were no HFRS cases, while 20 people in a similar unvaccinated group of 2,000 got sick. Even so, blood tests show that antibodies from the vaccine fade over time, so experts still argue about how long protection really lasts.
There is also a problem of coverage. Hantavax targets the Hantaan virus. It does not provide strong protection against many other hantaviruses found in Europe and the Americas. A vaccine that works in South Korea does not protect against the Puumala virus in Finland, the Dobrava virus in the Balkans, or the Andes virus in Argentina. Hantaviruses as a group are diverse. Hantavax was an important first step, .
The Four Corners and the Question Nobody Was Asking
In May 1993, . Just days before, his fiancée had died in the same way. Teams from the Indian Health Service, the New Mexico Department of Health, and later the Centers for Disease Control and Prevention (CDC) investigated. They found an outbreak of a severe, new lung disease among Navajo people in the Four Corners region, where New Mexico, Arizona, Colorado, and Utah meet.
Within a few weeks, the CDC traced this new illness to a hantavirus carried by deer mice (Peromyscus maniculatus). The virus came to be called the . The disease it caused was named hantavirus pulmonary syndrome (HPS). Unlike the Korean form, which mainly damages the kidneys, HPS attacks the lungs. In the early years, about 4 out of every 10 people who got it died. (It was named “Sin Nombre,” which is Spanish for “No Name,” because the local authorities did not want to name it after the location where it was found.)
The Four Corners outbreak changed how scientists thought about hantaviruses in the Americas. Over the next few years, they identified more than a dozen different hantaviruses in North and South America. The outbreak also exposed a gap that Hantavax was never designed to fill: there was no vaccine for any of these New World hantaviruses that cause HPS.
As of 2026, this is still the case, and the reasons have more to do with money, logistics, and numbers than with lab science.
The Commercial Problem No One Could Solve
To get a vaccine approved, you usually need two things: enough cases to test it in a large trial, and a big enough future market to convince funders and companies to invest. Hantavirus has struggled on both counts.
By the end of 2023, . That is 30 years of surveillance and fewer than 900 cases total. A vaccine trial that proves protection would need thousands of volunteers who live in higher-risk areas and would need to follow them for years, waiting to see who gets sick. Because HPS is rare and unpredictable, it would take a long time and a lot of money to reach clear results. In 2012, r, with no guarantee that companies would ever earn that money back.
For many years, the National Institute of Allergy and Infectious Diseases (NIAID) at NIH has listed , meaning they are taken seriously as possible causes of large outbreaks or bioterrorism events. That label shows concern about what could happen if things change. But for much of the time since 1993, the actual funding available for hantavirus vaccines did not match the level of concern on paper, so vaccine efforts moved slowly or stopped.
DNA Vaccines: Progress in the Pipeline
The most consistent work toward a hantavirus vaccine in the United States has come from scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), . Their strategy uses DNA vaccines. Instead of giving people a weakened or killed virus, . Human cells use those instructions to briefly make the viral proteins, which then train the immune system.
Because these vaccines do not contain live virus, they do not require the same high-level safety labs that work with the full, living hantavirus. They also focus on a part of the virus (the so‑called M gene) that can be swapped out and updated as new strains appear.
. No serious side effects were reported. When researchers used a needle‑free device called the PharmaJet Stratis® system to deliver the vaccine, everyone in the Hantaan group and everyone in the Puumala group developed neutralizing antibodies. A later, slightly larger Phase 2a trial tested a combined Hantaan/Puumala vaccine. Another Phase 1 trial tested a DNA vaccine against the Andes virus with 48 volunteers.
These are strong early signals. But these vaccines are still in the early and middle steps of testing. Phase 2 studies look at safety and immune response in more people. Phase 3 trials, which actually test whether a vaccine prevents disease in the real world, have not happened yet. The basic barrier remains: finding enough people at enough risk to run a meaningful Phase 3 trial for a rare disease.
2026: New Tools, Old Problem
In early 2026, two different projects changed what is possible in hantavirus vaccine design, even though they did not immediately solve the problem of how to test a vaccine in the field.
In March 2026, a team at the University of Texas at Austin, working in a group called PROVIDENT (part of NIH’s ReVAMPP program [Research on Vaccines, Antibodies, and Medicines for Pandemic Preparedness]), . They focused on the Gn–Gc tetramer in its “pre‑fusion” shape, meaning the shape it has before it fuses with a human cell. That matters because many modern vaccines work best when they freeze a virus protein in this early shape and train the immune system to recognize it. With this atomic‑level map, the UT Austin team designed an experimental vaccine that, when tested in mice, produced neutralizing antibodies against the Andes virus.
In a separate effort, . The center shared hantavirus genetic sequences with Moderna, and Moderna sent back test mRNA vaccine materials. The goal is a “broad” vaccine that protects against several hantavirus strains, not just one. Because mRNA vaccines can be redesigned quickly by swapping in new genetic code, they offer a faster way to respond to new hantaviruses than traditional vaccines based on killed virus.
At the same time, the : an mRNA shot, a protein‑based vaccine, and a vaccine that uses Newcastle disease virus as a carrier. All three are being designed for use as nasal sprays or drops, to build immunity directly in the nose and lungs, where hantavirus does its most dangerous damage.
The Cruise Ship and the Urgency Question
In May 2026, . The World Health Organization is now looking closely at whether the virus spread from person to person on the ship, not just from contact with rodents.
As of May 2026, the odds are low that a hantavirus vaccine will be licensed this year. This is not surprising when you know that there are no Phase 3 trials underway, and vaccine development does not move that fast. What the Hondius outbreak has changed is visibility and urgency. Hantavirus is no longer just a rare rural infection tied to deer mice or rice rats. It is now linked to an outbreak on a ship that traveled to 23 countries, involving passengers from many parts of the world.
This is exactly the kind of scenario the NIH ReVAMPP program was created for: viruses that have been understudied, have weak or no medical tools, and have not attracted much funding, but could cause serious trouble if conditions change. The detailed Andes virus structure was published in early 2026, the DNA vaccine data already collected, and the mRNA platforms being developed with companies like Moderna give scientists real tools to work with—if governments and companies decide to invest in moving them forward.
What Professor Ho Wang Lee Started
died on July 5, 2022, at age 93. By then, Hantavax had been used for more than three decades. His Hantavirus Research Cooperation Center at Korea University, supported by the World Health Organization, had trained many virus researchers. The hantavirus group he named had grown to include dozens of strains found on every continent where people live.
Lee never solved the New World hantavirus problem. No one has. But his path is the same path that researchers are still following: find the virus, study its structure, build an antigen, raise an immune response, test it in people, and only then approve it.
The early steps—finding viruses, mapping their proteins, and designing vaccine candidates—are now faster and more precise than ever. The hardest step is still the last one: proving that a vaccine works against a disease that appears rarely, and mostly in scattered communities. The current outbreak may finally push the world to take on that challenge.