Antibodies from a test tube
Scientists have simplified and accelerated the production of human antibodies
Oleg Lischuk, N+1
British and American scientists have developed a method for the simple and rapid production of specific human antibodies in vitro. The results of the work are published in The Journal of Experimental Medicine (Nandin et al., Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies).
In the body, B-lymphocytes are responsible for the production of antibodies (immunoglobulins). When encountering an antigen of an infectious agent in the blood, such a lymphocyte proliferates into a plasma cell, which begins to produce specific antibodies to this antigen. The proliferation is triggered under the control of a cascade of intracellular signaling pathways and is accompanied by interaction with T-lymphocytes; activation of toll-like type 9 receptors (TLR9) of B-lymphocytes plays a key role in this process.
The most common method of stimulating the synthesis of antibodies against specific infections is vaccination, in which a purified antigen is injected into the body and they wait for it to produce a sufficient amount of antibodies. This method, despite its proven high effectiveness, has a number of contraindications, is available for a limited number of infections and is suitable only for the prevention, not the treatment of diseases. Therefore, therapeutic antibodies have to be obtained outside the patient's body.
In laboratory conditions, the proliferation of B lymphocytes isolated from the patient's blood into plasma cells in the presence of a given antigen can be started using synthetic TLR9 ligands - oligodeoxynucleotides CpG (short DNA fragments containing cytosine and guanine). In the classical form, this process is lengthy and laborious, since CpG causes the proliferation of all cells, and a limited number of B lymphocytes interact with the antigen, and the resulting plasma cells producing the required antigens must be separated from the rest.
To ensure specific cell proliferation, researchers at the Francis Crick Institute, the Ragon Institute of the Massachusetts General Hospital and other research centers have developed nanoparticles from streptavidin coated with a given antigen and CpG. Treatment of B-lymphocyte culture with such nanoparticles leads to the activation of TLR9 and, as a result, proliferation of only those cells that have recognized the antigen.
During the tests of the technique on B-lymphocytes of healthy donors, the researchers managed to obtain significant amounts of specific antibodies within a few days, including tetanus toxoid, antibodies to hemagglutinin of several types of influenza A virus and human immunodeficiency virus envelope protein gp120. When interacting with the corresponding antigens, such antibodies effectively bound and neutralized them.
"This is a new and valuable approach not only to the rapid production of therapeutic antibodies, but also to accelerate the development, testing and characterization of new vaccines without the need for time–consuming, lengthy and expensive clinical trials," the authors write.
Therapeutic antibodies are promising drugs for the treatment of a number of infectious and oncological diseases. Under experimental conditions, they demonstrated high efficiency against HIV, Marburg fever and many other diseases.
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26.07.2017