The deadly hantavirus outbreak aboard the cruise ship MV Hondius has put the spotlight on a rare pathogen that typically attracts relatively little attention, even from scientists.
There are no targeted treatments for hantaviruses, which are typically carried by rodents, and no widely available vaccines. So when passengers began falling ill in the middle of the Atlantic Ocean, doctors and public health experts were limited in what they could offer.
“It’s kind of a wake-up call,” said Dr. Vaithi Arumugaswami, an infectious disease researcher at the University of California, Los Angeles. “Our tool kit is almost empty.”
That’s not for lack of trying. A handful of scientific teams around the world have been working — for decades, in some cases — to develop hantavirus treatments and vaccines. But it has not been easy to find funding or nurture commercial interest in medical interventions for a type of pathogen that does not infect humans often and does not spread easily between people.
“It’s not an airborne, highly contagious viral threat, so it hasn’t been as high a priority for groups trying to prevent pandemics,” said Jay Hooper, a virologist at the United States Army Medical Research Institute of Infectious Diseases.
But there are promising vaccines and treatments in development. And some of them, experts said, could be moved through the pipeline rapidly if hantavirus interventions became a priority.
“I do think there are things that are sitting there on the bench that could be quickly developed,” said Dr. Ronald Nahass, the president of the Infectious Diseases Society of America. “But nothing is ready.”
Vaccine development
There are two main types of hantaviruses: Old World viruses, which circulate primarily in Asia and Europe, and New World viruses, which are found in the Americas. The cruise ship outbreak has been linked to a New World virus known as the Andes virus, which is endemic to South America and is the only hantavirus known to spread between people.
There are vaccines that target some of the Old World viruses in Asia, but their efficacy is modest, experts said. And there are no licensed vaccines for the New World viruses, which include the Sin Nombre virus endemic to rodents in the western United States.
But there are some in development. Dr. Hooper and his colleagues have developed a DNA vaccine for the Andes virus, which proved promising in a small phase 1 trial. Under certain dosing regimens, the researchers found, more than 80 percent of participants produced neutralizing antibodies. “It’s pretty amazing,” said Dr. Hooper, who is an inventor on multiple hantavirus vaccine patents owned by the U.S. government. “Getting these kinds of neutralizing antibodies in humans is impressive.”
There were drawbacks, including that the vaccine seemed to require at least three doses. But the vaccine is ready for further development “if there’s a need,” Dr. Hooper said. “We’ve done the science. It’s just other forces that are required to move vaccines forward — markets, government demand.”
Other teams have potential vaccines in earlier stages of development. For instance, Bryce Warner, a hantavirus researcher at the University of Saskatchewan, and his colleagues are exploring a variety of approaches, including a nasal vaccine that they hope might spark a more robust immune response in the airway.
But the research, which is being conducted in hamsters, is still in early stages, and hantavirus vaccine candidates can be challenging to move forward. Scientists lack good large-animal models for hantaviruses, Dr. Warner said, and human cases are rare enough to make trials tricky. “It’s very difficult to conduct a clinical trial when you only have a limited number of cases annually,” he said. “You don’t have the numbers of people to really show a robust effect.”
Drug hunting
Currently, the primary treatment for hantavirus infection is supportive care, which may include supplemental oxygen or heart-lung bypass machines. Doctors also sometimes prescribe an existing antiviral drug, called ribavirin, but there is not strong evidence that it is effective for New World viruses, scientists said.
The hunt for new drugs is underway, though. At U.C.L.A., Dr. Arumugaswami and his colleagues found that favipiravir, an antiviral approved to treat influenza in Japan, inhibited the Andes virus in human cells. They also identified several compounds that had broad antiviral activity, blocking hantaviruses as well as other types of viruses, in human organoids, miniature clusters of tissue that mimic the function of organs.
Other teams have been working to develop therapeutic antibody treatments, often working from blood samples collected from hantavirus survivors. “We were able to isolate the natural antibodies that people are making and basically winnow them down and find one that was really good,” said Kartik Chandran, a virologist at the Albert Einstein College of Medicine in New York. “We actually found several.”
When Dr. Chandran and his colleagues tested these antibodies in hamsters, one produced especially encouraging results: It seemed to work against both Old and New World hantaviruses and was effective even when given relatively late in the course of infection, Dr. Chandran said.
(Dr. Chandran is listed as an inventor on patents for hantavirus antibodies.)
Several other teams have also produced antibodies that were broadly effective in small animals, but that is where a number of potential products have stalled, experts said.
“We have a lead drug, and now what we need is someone to pay the money, which would be something like $40 million, to go the next step,” said Dr. James Crowe, director of the Vanderbilt Center for Antibody Therapeutics. “We have neither government nor foundation nor company support to do that. So we’re just waiting to find a partner.”
(Vanderbilt University has applied for patents related to these antibodies; Dr. Crowe is listed as the inventor.)
Experts said that they hoped the current outbreak might help bring attention to a family of often-overlooked viruses.
“Certainly judging by just my inbox and text messages, there’s a renewed interest in these agents, and renewed interest in maybe at least revisiting where they are in the priority list,” Dr. Chandran said.
Whether that interest can be sustained after the virus fades from the headlines remains to be seen, experts acknowledged.
“Raising awareness never hurts,” Dr. Warner said. “We’ll see whether or not it leads to anything tangible, at least in terms of funding and resources for advancing some of these things that are lacking for hantavirus.”
