By genetically engineering immune cells to make more effective antibodies, they have defended mice from a potentially lethal lung virus. The same strategy could work in humans against diseases for which there are no vaccines.
“It’s a huge breakthrough,” says Immunologist James Voss of the Scripps Research Institute in San Diego, California, who wasn’t connected to the study.
Vaccines typically contain a disabled microbial invader or shards of its molecules. They stimulate immune cells known as B cells to crank out antibodies that target the pathogen. Not everyone who receives a vaccine gains protection, however. Some patients’ antibodies aren’t up to snuff, for instance. And researchers haven’t been able to develop vaccines against some microbes, such as HIV and the respiratory syncytial virus (RSV), which causes lung infections mainly in children and people with impaired immune systems.
In the new study, immunologist Justin Taylor of the Fred Hutchinson Cancer Research Centre in Seattle, Washington, and colleagues tested whether they could engineer B cells to recreate an antibody already known to be potent against RSV. With the DNA-snipping CRISPR genome-editing system, they cut one of the antibody genes in mouse B cells. The scientists then used a virus to ferry a gene for the anti-RSV antibody into the cells. After the inserted gene settled into position in the sliced DNA, it began to work, and the B cells churned out the RSV-targeting antibody. Using the same approach, the scientists could also prod human B cells to create antibodies against three other viruses, including HIV and one type of influenza virus. “We got amazingly high efficiencies,” says Taylor, with up to 60% of cells manufacturing the added antibody, higher than in previous studies that attempted to engineer B cells.
To determine whether transplanting the modified cells could prevent infections, the scientists injected the genetically engineered B cells or control cells into mice and then exposed the animals to RSV. Five days later, the lungs of the control mice teemed with the virus. But the lung of mice that had received the engineered cells contained almost no RSV, the researchers reported recently in Science Immunology. And when the researchers injected the modified B cells into mice with defective immune systems—a common problem in bone marrow recipients, who are susceptible to RSV—the rodents were able to fight off the virus 82 days later.
No HIV vaccine exists, but a few people exposed to the virus naturally produce extremely potent antibodies against it. The B cell approach might allow researchers to harness these antibodies and thus provide protection against HIV infection. Engineering the cells to make different antibodies might fend off other diseases caused by viruses that have evaded vaccines.
“This is an important paper,” says immunoengineer Michael Goldberg, CEO of the biotech startup STIMIT in Cambridge, Massachusetts. He’s optimistic that cells will eventually be used in people. “Hopefully, children will one day go to their pediatrician’s office to receive engineered B cells that express the best-known antibodies for protection against most strains of certain viruses.”
But genome engineer, Branden Moriarity of the University of Minnesota in Minneapolis suggests the approach may be so expensive—cancer treatments that rely on other engineered immune cells cost hundreds of thousands of dollars—that it won’t be practical. “People will not be using engineered B cells prophylactically in the near future.”
By Chigbu Nwaobia