Immunity without vaccines
Immune cells armed against difficult viruses
Kirill Stasevich, Science and Life (nkj.ru ) based on the materials of Hutch News: Engineering vaccine-like protection without a vaccine.
Vaccines teach the immune system to recognize dangerous microbes before they enter the body. Immune cells are shown either weakened pathogens, or some molecules by which they can be recognized - and the immune system remembers them.
This means that now we have a group of immune cells that, if anything, will immediately begin the synthesis of antibodies against a virus or a bacterium. The necessary antibodies do not have to be picked up for a long time, the only thing is that the cells synthesizing them quickly wake up and multiply.
But it is not possible to create sufficiently effective vaccines against some pathogens. For example, there are still no vaccines against HIV, influenza virus, respiratory syncytial virus that causes respiratory tract infection. This is because viruses can change very quickly, and the vaccine that protected against influenza a year ago will no longer be effective next year: the virus has changed the molecules by which immune cells recognized it earlier.
On the other hand, viral proteins have areas in their molecules that must remain unchanged, otherwise the virus will not be able to infect cells and multiply. Therefore, recently researchers have been actively looking for methods by which immunity could be trained on such important molecular structures. Actually, the immune system itself eventually begins to synthesize antibodies against unchanging fragments in viral proteins, but this happens too late, and such antibodies are synthesized not very effectively – that is, immunity needs to be helped here.
Staff Cancer Research Center named after Fred Hutchinson suggests a radical way – you don't need to make any vaccines, you just need to use genetic engineering to supply immune cells with the genes of the right antibodies. We know how antibodies are made, we know which areas in their molecules are responsible for the recognition of foreign proteins, and we know what antibodies aimed against a particular viral protein should look like.
The method that allows you to edit cellular DNA with great accuracy is the well–known CRISPR/Cas. Its essence is that an enzyme is injected into the cell, which cuts into the DNA in a strictly defined place. The cell has to repair the damage, but it corrects it according to a template – a piece of DNA that is injected into it along with the enzyme that cut its own DNA.
What needs to be done so that the immune system can synthesize antibodies against some "non-vaccinable" virus? It is necessary to take a portion of B-lymphocytes and edit their genes encoding immunoglobulins so that they recognize conservative sites of viral proteins. This is exactly what Justin J. Taylor and his colleagues did.
For the experiment, they took mouse and human B cells in which the genes of immunoglobulins were edited using CRISPR/Cas to produce antibodies against HIV, or influenza, or Epstein-Barr virus, or respiratory syncytial virus - all four belong to difficult viruses in the sense of the impossibility of creating a vaccine against them. Then the cells were given a meeting with real viruses, and they really began to synthesize the necessary antibodies.
But will such B cells be effective in the body? To find out, mouse B-lymphocytes with antibodies against respiratory syncytial virus were injected back into mice, which were then infected with the virus. After five days, animals with edited B-lymphocytes had almost no virus left, but ordinary mice without edited B-lymphocytes had very, very much of the virus.
Moreover, such B cells effectively protected from infection even those mice that, due to the mutation, had almost no T- and B-lymphocytes of their own. Of course, this method does not provide lifelong immunity yet (the lifetime of B-lymphocytes is several weeks), but the experimental mice were protected from infection for at least 82 days.
The experimental results are described in Science Immunology (Moffet et al., B cells engineered to express pathogen-specific antibodies protect against infection). This is not the first attempt to teach the immune system to synthesize the necessary antibodies by simply providing the immune cells with the appropriate genes, but this time the authors of the work managed to avoid some of the problems that arose in earlier studies (for example, now the immunoglobulin genes were edited so as to eliminate the likelihood of autoimmune reactions). In the future, such cells can be useful not only in the fight against viruses, but also in other diseases where antibodies are needed from the immune system, which for some reason it does not synthesize.
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