We can help the body fight entire viral families

LA JOLLA, CA—Scientists at La Jolla Institute for Immunology (LJI) have discovered that combining key vaccine ingredients could give the body the tools it needs to fight the entire family of arenaviruses with a single vaccine. This “pan-arenavirus” vaccine approach may protect against life-threatening infections from Lassa virus, Junin virus, and many other arenaviruses with pandemic potential.

"We are now moving toward the next steps of designing vaccines and seeing which formulations may work best," says LJI Professor Alessandro Sette, Dr.Bio.Sci.

This research comes as scientists are working to stop the spread of Andes hantavirus, which recently caused a deadly outbreak among cruise ship passengers and crewmembers. Hantaviruses and arenaviruses are very similar in how they spread (between rodents and humans) and how they work (both are single-strand, segmented RNA viruses). 

In their Cell Reports Medicine paper, the researchers show that T cells can spot the family resemblance between different species of arenaviruses. Harnessing these "cross-reactive" T cells is critical for designing "pan-viral" vaccines that combat many viruses at once.

"We can apply this new research approach to multiple viral families, no matter how rare they are in the human population," says LJI Research Assistant Professor Alba Grifoni, Ph.D., who co-led the study, with funding from the National Institutes of Health and the Coalition for Epidemic Preparedness Innovations (CEPI).

Investigating a dangerous viral family

Arenaviruses are most common in West Africa countries, where the deadliest arenavirus is called Lassa virus. This virus is spread by a species of rodent, called the multimammate rat. 

Lassa virus kills by causing severe, flu-like symptoms, which can lead to bleeding from the mouth or gastrointestinal tract. The virus kills between 5,000 and 10,000 people each year and hospitalizes many more.

And Lassa virus has several dangerous relatives. The arenavirus family is known for its pandemic potential. Eight arenavirus species are known to cause disease in humans, and there are dozens of other arenaviruses that spread in animal populations.

About 45,000 years ago, arenavirus evolution diverged, leading to marked differences between "Old World" arenaviruses (in European, African, and Asian countries) and "New World" arenaviruses (in the Americas).

For the new study, LJI scientists examined whether T cells could "cross-react" between Old World and New World arenavirus species. After thousands of years, could T cells still spot the family resemblance?

Answering this question is key to pandemic preparedness. 

"Animals carry many viruses, and only some of these viruses will acquire the ability to infect humans and cause an outbreak," says Grifoni. "It's hard to predict which emerging virus might cause disease, which is why it is important to study T cells. "So why do we want to look at T cells? T cells are good at recognizing viruses, even if a virus is mutating."

Taking on Old World arenaviruses

First came an encouraging discovery—the scientists found that human T cells have the ability to cross-react to epitopes shared by all Old World arenavirus species. Epitopes are sites on a virus that T cells can recognize as a sign of infection. Sette and Grifoni found that Old World arenaviruses have shared, or "conserved," epitopes.

That means a vaccine against Lassa virus could potentially also protect against the Old World Lujo virus and lymphocytic choriomeningitis virus (LCMV) for example. In fact, there are already experimental Lassa virus vaccines under development that can induce T cells able to target these shared epitopes that are similar within the Old world viral family.

T cells that targeted Old World arenaviruses did not cross-react to New World arenaviruses. It appears the two groups of viruses are too different and don't share the same epitopes.

New World, new epitopes

It was time to learn more about New World arenavirus epitopes. The scientists began by analyzing T cell responses to Junin virus, an arenavirus that causes Argentine hemorrhagic fever. Some people in Argentina have received a vaccine against Junin virus, which means their bodies have already produced T cells to fight infection. 

In work spearheaded by LJI Postdoctoral Associate YeiI Lee, Ph.D., the scientists discovered that certain T cells that target Junin can cross-react to other New World arenaviruses.

This discovery gives LJI researchers a potential path for developing a broad, "pan-arenavirus" vaccine. Every vaccine includes an immunogen, an ingredient such as a protein or peptide that sparks an immune response against a vulnerable piece of a pathogen. The new study suggests that a future vaccine should include two immunogens: one from an Old World arenavirus and one from a New World arenavirus.

By combining this virus-fighting weaponry, scientists could develop a vaccine that directs T cells to fight every type of infective arenavirus we know of. This broad T cell activity might even help us fight arenaviruses that emerge from animal reservoirs in the future.

Responding to hantaviruses

Lassa virus and Junin virus aren't part of daily life here in the United States—but hantaviruses are becoming more and more of a local concern. Hantavirus is carried by rodents here in California. According to the California Department of Public Health, risk of infection is low, but people should take steps to avoid rodent dropping and contaminated areas.

Recently, attention has turned to the risk of person-to-person hantavirus transmission. In May 2026, an outbreak of the Andes strain of hantavirus sickened 14 and killed three people on an international cruise ship.

Like arenaviruses, hantaviruses are primarily spread by rodents. The Andes hantavirus, which recently spread on the cruise ship MV Hondius, appears to have the unique ability to spread from human to human. 

Also like arenaviruses, hantaviruses are split into Old World and New World species. Importantly, both arenaviruses and hantaviruses are known as single-strand, segmented RNA viruses, which means they carry similar genetic instructions.

Sette says the new study shows how scientists can analyze T cells to devise life-saving vaccine strategies against arenaviruses, hantaviruses, paramyxoviruses (such as measles), togaviruses (such as Chikungunya), and many other threats.

The Sette and Grifoni labs have received important funding from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) and from the Coalition for Epidemic Preparedness (CEPI) to lead research toward pandemic preparedness. Each study brings the LJI team closer to developing rapid response tools to analyze viruses and combat future outbreaks.

"LJI is chipping away and generating data for many different viral families of concern," says Sette. "This research lays the foundation for future studies when one might, God forbid, have to move quickly."

Authors of the study, "Decoding the Human CD4+ T cell Epitope Repertoire For Lassa Fever Virus Reveals Novel Pan-mammarenavirus Vaccine Candidates," included Leila Siddiqui, Alison Tarke, Margaret Kim, Tanner Michaelis, Mariah Macias, Elizabeth Phillips, Simon Mallal, Raphael Trevizani, April Frazier, Richard H Scheuermann, Abril Zuniga, Christian Zmasek, Kevin Spurgers, Gideon Akintunde, Spencer W. Stonier, Talita Bianca Gagliardi, Kelly Warfield, Haoyang Li, Kathryn M. Hastie, Erica Ollmann Saphire, and Gene S Tan.

This study was supported by the National Institute of Allergy and Infectious Diseases and the Intramural Research Program, both of the National Institutes of Health, under awards number 75N93024C00056, U19 AI142790, and R21 AI180853; and by CEPI through the CEPI Immunogen Design for Disease X program.