Why CRISPR may work when vaccines don't

Researchers are using the gene-editing tool CRISPR to skip a step in antibody production in hopes of turning patients' immune systems against viruses that have no vaccines, STAT reports.

Vaccines work by inducing the immune system's B cells to manufacture antibodies against specific molecules — called antigens — that come out of a virus. 

Despite decades of attempts, no vaccines exist for deadly viruses such as HIV, respiratory syncytial virus and the cancer-causing Epstein-Barr virus. There are many reasons why these vaccines don't exist, including how difficult it is to identify the exact piece of an antigen that will lead to the production of an effective antibody.

Even when vaccines exist, they don't work when B cells fail to rearrange their DNA segments to create the needed antibodies.

This issue gave immunologist Justin Taylor, PhD, of Fred Hutchinson Cancer Research Center in Seattle, an idea — skip the vaccine.

For instance, injecting antibodies directly has been shown to protect premature babies against respiratory syncytial virus. Antibodies against several HIV strains control viral load in people with HIV, said Trevor Mundel, PhD, president of global health at the Bill and Melinda Gates Foundation.

However, the antibodies usually last only about 21 days and therefore must be given to patients multiple times. This prompted Dr. Taylor and his colleagues to try creating a therapy that could be done one time, using CRISPR technology to genetically reprogram B cells to produce and keep producing the antibody a patient needs.

In a preprint of a study submitted to a journal for peer review, Dr. Taylor and his colleagues said using CRISPR to edit B cells could produce "immunity against pathogens for which traditional vaccination has failed."  

A competing research team also saw promising results. In B cells from three donors, researchers edited the genome so it produced an antibody against HIV, they reported in eLife last month. The antibody attached itself to one of the HIV's antigens, which is the first step toward triggering the immune system to kill the virus.

There is a long way to go before reprogrammed B cells can give anyone immunity, but experts say the technology is promising.

"We can see gene editing [to protect against viruses] becoming feasible," said Dan Wattendorf, MD, director of innovative technology solutions at the Gates Foundation. "It's a very interesting time."

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