hantavirus particles to the cell membrane, seen through an electron microscope.
Scott Camazine / Science Source
Humans have used antibody therapies to treat infectious diseases for over 100 years. The blood plasma of the survivors of influenza administered to patients in 1912 may have contributed to their dramatic turnaround. In the years that followed, the immune proteins of the survivors were administered to infected people in an attempt to fight against diseases such as Lassa fever, SARS and even Ebola.
It is difficult, however, to find survivors who can donate plasma containing these lifesaving immune proteins. Now a team led by researchers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland, used genetically cows to produce large quantities of human antibodies against hantavirus engineering, an often fatal disease transmitted primarily rodents to people. In animal models, at least, these antibodies provide robust protection against the virus, opening the door to therapies to treat and prevent Hantavirus, for which there is no cure. The technique of bioproduction also holds promise for generating antibodies against other infectious agents.
The work is preliminary and needs to be tested in people, but the team called a "proof of concept" that human antibodies can be grown in animals and retain activity against the disease.
"I am personally very excited about it. I think it has potential for the treatment of patients with hantavirus infection, "says Greg Mertz, an infectious disease specialist at the University of New Mexico, Albuquerque, who was not involved in the research . "If we extrapolate this to other diseases, there where this approach could be promising."
The USAMRIID researchers led by virologist Jay Hooper, teamed with SAB Biotherapeutics in Sioux Falls, South Dakota, using genetically cows, when presented with an antigen, could produce fully human polyclonal antibodies against both the hantavirus strain Sin Number, first isolated from the Four Corners region of the southwest of satays and the Andes hantavirus strain that is prevalent in Chile. there, it infects an average of 55 people a year and kills about a third of them. After a long incubation period and a few days of fever and pain muscle, the virus attacks the lungs and often causes acute respiratory failure leading to death. There is no cure and experimental vaccines would be logistically difficult to use, even if they have passed clinical trials.
Creating human antibodies in an animal model is no small feat. Scientists combined parts of the human chromosome 14 and human chromosome 2 - bits that are needed to produce antibodies - in an artificial chromosome implanted in cows. The genes responsible for producing antibodies of the cow were silenced. Accordingly, cattle produced immune cells that spew human antibodies.
The DNA vaccines of then administered scientific experimental hantavirus against the Andes strains and Sin Nombre, cows "of transchromosomal". Within a month, the animals produced liters of high concentration of human antibodies against both strains. The scientists then extracted the immune proteins and used to treat hamsters who had been fatally infected with hantavirus. The treatment increased the survival of hamsters significantly, saving seven of eight infected Chilean hantavirus strain, while eight controls are dead, the team reports online today in Science Translational Medicine . Five of the eight hamsters infected with Sin Nombre strain were saved.
Animal models do not always translate to humans, but in this case, the research team is optimistic. non-human antibodies, for example, birds and primates have been safely administered to people in the past, and human antibodies should prove safe in 1 clinical trial phase, said reproductive physiologist Eddie Sullivan SAB Biotherapeutics, who led the development project transchromosomal the cows. And he suspects that the antibodies cease to function in humans. If anything, they can work better because they will be able to communicate with human immune cells most commonly, he said. "We expect that the antibodies are likely to be very well tolerated in humans and will respond similarly," says Sullivan.
Of course, nothing is certain. In very rare cases, some antibody therapies previous actually helped viruses replicate in cells in serving as a bridge to host cells. "in order to really complete the proof of concept clinical studies in humans showing the need for security to carry out" Hooper said. "If this material proves to be as easy to produce as it seems, and it is safe, I think it's a great, great way to move forward."
Scientists are also studying USAMRIID cut bovine intermediate and just give hantavirus vaccines directly to people. However, antibody therapies are actually more practical in some respects. In diseases such as hantavirus, when so few people are infected each year, a large-scale vaccination program might not make much sense, especially economically, said Hooper. Having a few doses of antibodies on hand to treat the unlucky few infected people could solve the problem without the need to vaccinate huge sections of the population. In addition, Sullivan noted, one cow may produce antibodies against different strains in abundant amounts, up to 1000 human doses per month.
A huge challenge for any potential treatment for hantavirus is to find a way to diagnose the disease in time. Infection is difficult to recognize before it moves to the lungs, at which point it is often too late. Having an available supply of hand hantavirus antibodies could allow health workers to administer treatment for people who have been in contact with an index case, said Mertz.
Again, the potential benefits still hinge on clinical trials that demonstrate the safety and efficacy; the team is optimistic that they could begin next year for hantavirus, and perhaps even earlier for other diseases. "We work on Ebola and also MERS-CoV," Sullivan said.
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