Scientists at La Jolla Institute for Immunology (LJI) are developing tools to fight hantaviruses, including the Andes strain of hantavirus, which recently caused an outbreak on the cruise ship MV Hondius.
LJI scientists recently shared a new analysis of how the immune system’s B cells respond to Andes hantavirus. Their report is encouraging. The scientists show that hantaviruses can spur a strong response from virus-fighting B cells. These B cells can then churn out antibodies to neutralize Andes hantavirus.
This analysis offers strong evidence that future vaccines and antibody-based therapies can boost the immune system’s fighting power, says LJI Professor Alessandro Sette, Dr.Biol.Sci.
“Because hantaviruses have a relatively long incubation period, we may have a window of opportunity to intervene and administer vaccinations or monoclonal antibodies to people who may have been exposed to hantaviruses,” says Sette.
For this new analysis, the LJI team conducted a meta-analysis of datasets in LJI’s Immune Epitope Database (IEDB), which is funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID).
The findings show why immune system research is critical for pandemic preparedness. The MV Hondius outbreak illustrates the critical need for new anti-viral therapies and vaccines that can help us respond quickly to outbreaks—no matter where they come from.
What makes Andes hantavirus a threat?
Hantaviruses are a family of zoonotic pathogens, which means they can spread between humans and animals.
Different species of hantavirus circulate in different parts of the world. In California, for example, the main hantavirus known to cause illness is called Sin Nombre virus, and it is primarily spread by deer mice.
Infections are rare, but it’s important to stay cautious. A person might be infected with a hantavirus when they come in contact with contaminated rodent saliva, droppings, or urine. For example, someone might sweep a barn or a cabin and send particles from rodent droppings into the air, creating a respiratory hazard.
Most hantaviruses don’t cause outbreaks because they cannot spread from person to person. These hantaviruses can spread from a rodent to a human, but they can’t jump from person to person.
The Andes hantavirus is different. Andes hantavirus was first identified in 1995, after an outbreak in the small city of El Bolsón in southern Argentina. This outbreak grew surprisingly quickly, even spreading outside El Bolsón.
By tracking these cases—and performing molecular analyses—researchers discovered that Andes hantavirus could spread from person to person. Andes hantavirus is still the only hantavirus we know of that is capable of person-to-person transmission, and the virus continues to cause periodic outbreaks in Argentina.
According to health officials, the Andes hantavirus outbreak aboard the cruise ship MV Hondius appears to have originated with an elderly couple who boarded the ship after touring areas of South America, including Argentina. It’s believed the couple may have been exposed to the virus while on a birdwatching tour.
How dangerous is Andes hantavirus?
Andes hantavirus isn’t as contagious as other viruses, such as measles, but it does have the advantage of stealth. According to the Mayo Clinic, a person can be exposed to a hantavirus and then not show symptoms for one to eight weeks. That long incubation period may help explain why the infected passengers were able to board the MV Hondius without causing concern.
What happens when symptoms do start to appear?
Again, geography is key when it comes to understanding hantaviruses. Hantaviruses are split into two groups: the “Old World” hantaviruses in Africa, Asia, and Europe, and the “New World” hantaviruses in North and South America.
These different hantaviruses can cause different symptoms. “New World” hantavirus infections can lead to hantavirus pulmonary syndrome, which feels like a severe flu. An infected person might then develop cardiopulmonary symptoms, such as shortness of breath, fluid in the lungs, and low blood pressure. It’s estimated that hantavirus pulmonary syndrome has a 50 percent mortality rate, according to the World Health Organization.
Old World hantaviruses can cause hemorrhagic fever with renal failure, which comes with breathing difficulty and low blood pressure, along with severe damage to the kidneys. These Old World hantaviruses are thought of as relatively more mild, with a 1 to 15 percent mortality rate.
Where are the hantavirus treatments?
We currently have no specific treatments for any hantavirus species present in North or South America. Instead, patients have to rely on supportive care, such as respiratory support, to help them survive.
But vaccine and treatment options are on the horizon. LJI scientists are working on new ways to harness our own immune responses to stop severe infections. To succeed, LJI researchers need to investigate immune responses to hantaviruses and many other zoonotic pathogens.
One of these notorious pathogens is Dabie bandavirus, a tick-borne virus that can cause a serious condition called severe fever with thrombocytopenia syndrome (SFTS). This virus, better known as SFTSV, belongs to the same viral order as hantaviruses, which means they are related fairly high up on the viral family tree.
LJI Research Assistant Professor Alba Grifoni, Ph.D., is studying how the body’s T cells recognize SFTSV and fight infection. She wants to find T cells that can recognize the more generic parts of SFTSV, the “conserved” molecular regions that SFTSV shares with its viral relatives.
Instead of hunting for T cells that specialize in fighting SFTSV, Grifoni is looking for T cells that have a broad response and can “cross react” to viruses that share a family resemblance.
“We are applying this strategy for SFTSV and will be prepared to ask the same questions for hantavirus,” says Grifoni.
A single vaccine against many viruses
In fact, cross-reactive T cells may be the key to stopping emerging diseases.
Take the family of arenaviruses, for example. Like hantaviruses, many arenaviruses are carried by rodents. In West Africa, rodents called multimammate rats can spread an arenavirus called Lassa virus. Like Andes hantavirus, Lassa virus can also spread from person to person.
“There are striking similarities between arenaviruses and hantaviruses,” says Sette. “While they are not part of the same viral family, these two viral families have a lot in common.”
Like hantaviruses, arenaviruses are also split into “Old World” and “New World” species. In a recent Cell Reports Medicine study, Sette and Grifoni studied how T cells spot the resemblance between these two groups of arenaviruses.
The scientists discovered that human T cells that responded to Lassa virus could also recognize all other Old World arenaviruses. They also found that T cells that recognized a New World arenavirus, called Junin virus, could “cross react” to all other New World arenaviruses.
Now scientists can use that knowledge to develop “pan-arenavirus” vaccines that train our T cells to target both Old and New World arenaviruses. [Read: We can help the body fight entire viral families] With just one vaccine, we could protect against Lassa virus, Junin virus, and all of their arenavirus relatives.
The future of life-saving medicine
LJI scientists are focused on pandemic preparedness. They say this same T cell research approach can also help us combat Andes hantavirus—and any hantavirus that might cross over from rodents to humans. “This research is very applicable and very current,” says Sette.
In fact, the Sette and Grifoni labs have begun to generate biological tools (called reagents) to detect T cell responses to hantaviruses. They plan to share these reagents with other collaborating laboratories.
Sette says this T cell research, together with the recent B cell analysis and antibody research led by outside labs, may lead to the first-ever vaccines and treatment options for hantaviruses.
“We have confidence that vaccines and perhaps monoclonal antibody therapies could be developed against hantaviruses,” says Sette.
The research cited in this article was supported through the National Institute of Health’s National Institute of Allergy and Infectious Diseases, through contract no. 75N93026C00001 to the IEDB; through the National Institute of Allergy and Infectious Diseases and the NIH Intramural Research Program under awards number 75N93024C00056, U19 AI142790, and R21 AI180853; and by CEPI through the CEPI Immunogen Design for Disease X program.
