A researcher at the Autonomous University of Madrid (UAM) together with scientists from the Scripps Research Institute of California (USA) developed a new genome engineering technique to generate human primary B cells that produce antibodies to neutralize or disable human immunodeficiency virus (HIV).
The technique could be used in the future to generate new vaccines or broad-spectrum therapies, not only against HIV but against other pathogens such as influenza and hepatitis, the authors of the study published in eLife.
B cells, also called B lymphocytes, are responsible for producing antibodies that can recognize and attack pathogens. Although the human body can produce billions of different antibodies, those that protect against HIV are rarely generated.
However there are protective antibodies against HIV. “A small percentage of patients with HIV naturally develop antibodies that can amply neutralize the virus,” explains Alicia González Martín, co-author of the study and researcher at the UAM.
“The technique we have developed edits the B-cell genome using CRISPR-Cas9 technology so that the cells produce the same neutralizing antibodies against HIV that have been found in some patients,” the researcher explains.
B cells edited and active
The authors showed that the edited B cells still had the ability to activate, divide and go through the maturation process whereby B cells modify their own antibodies to produce more effective antibodies.
As part of the work, the scientists also used human B cells that had been purified from the blood of three healthy donors. They showed once again that the edited B cells perform their normal function and produce antibodies against HIV.
Currently there are immunotherapies against cancer in which scientists isolate patients’ T cells, genetically alter them to recognize cancer cells and return them to the bloodstream of patients to fight tumors. The new work provides the first proof of concept that a similar approach could work with B cells and infectious diseases.
More work is needed to demonstrate that the edited B cells will work to fight pathogens in an animal model, or even in humans.
“Such cells could potentially be used in preventive approaches such as a vaccine or for treatment. The next experiments will prove whether these edited cells can produce protective antibodies against HIV in response to vaccination in mice,” González Martín concludes.