Researchers may have come up with a new way for the body to manufacture helpful proteins - including certain highly potent but hard-to-produce antibodies - by reprogramming the immune system.
Traditional vaccines prompt immune cells called B cells to produce antibodies that recognize germs. Some viruses, however, such as the human immunodeficiency virus that causes AIDS, can shield their most vulnerable regions behind sugar molecules that resemble the body's own tissues and are largely ignored by the immune system.
So-called broadly neutralizing antibodies can circumvent these shields, but they arise from rarely produced cells only after a long and complex process of mutation. Most people will never produce them even if they are exposed to the antigens through careful vaccination regimens, the researchers explained in the journal Science.
The researchers wondered whether they could permanently install instructions for broadly neutralizing antibodies in the stem cells that give rise to B cells. If those stem cells were programmed correctly, every B cell they later produced would carry the same blueprint for producing broadly neutralizing antibodies, ready to be activated by vaccination.
As a proof of concept, the team used CRISPR gene-editing tools to insert the genetic blueprint for producing the rare, protective broadly neutralizing antibodies directly into immature stem cells and injected the cells into mice. These stem cells later developed into B cells programmed to produce the engineered antibody.
Only a few dozen edited stem cells transplanted into the mice were necessary to trigger production of large amounts of broadly neutralizing antibodies that persisted long-term.
The approach was successful at generating antibodies against HIV, influenza and malaria, according to a perspective article published with the report.
Human stem cells edited using the same approach also gave rise to functional immune cells, suggesting the approach might one day work in people, the researchers said.
Study leader Harald Hartweger of Rockefeller University sees potential uses down the road for the technology for a wide variety of health issues.
"HIV antibodies, of course, but also solutions that address protein deficiencies and metabolic disease, as well as an antibody to treat inflammatory disease or the flu, or one for cancer," he said in a statement. "This is a step in that direction, showing the feasibility of making life-saving proteins."
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