Comprehensive coverage

New research may advance the development of vaccines to be given orally

The possibility arises from the disclosure of the "training programs" of the cells of the immune system in the intestine

Lymphoid organ in the small intestine. In red: accumulations of type B immune cells within the "training sites". In green - cells secreting antibodies after leaving the training sites and migrating to the intestinal tissues. Courtesy of Prof. Ziv Shulman, Weizmann Institute
Lymphoid organ in the small intestine. In red: accumulations of type B immune cells inside the "training sites". In green - cells secreting antibodies after leaving the training sites and migrating to the intestinal tissues. Courtesy of Prof. Ziv Shulman, Weizmann Institute

Vaccination rates among different populations are at the center of public debate following a renewed outbreak of diseases that seemed to have disappeared from the world, at least in some developed countries. Most of the vaccines available on the market today are given by injection - and only a few of them are given orally. Besides the ease of use of vaccines that do not require subcutaneous or intramuscular injection, orally administered vaccines may provide better protection against disease agents that enter the body through mucosal tissues (gastrointestinal, respiratory, and reproductive tracts). However, one of the main difficulties facing the development of oral vaccines is the unique conditions prevailing in the intestine. Weizmann Institute of Science scientists recently studied the activity of the cells of the immune system in the intestine with the help of an innovative method that allows imaging of whole organs and mapping of all the cells of the immune system within them; Their findings, published today in the scientific journal Nature Immunology, may make it possible to expand the use of oral vaccines.

Whether by injection, drops or pills, the purpose of vaccines is to give the body effective and long-term protection through exposure to weakened or killed pathogens that do not endanger the body. Immune protection is made possible thanks to the nature of the activity of the cells of the immune system called B cells, each of which "knows" how to secrete a specific antibody suitable for a specific purpose. When the body is exposed to a molecule that triggers an immune response (antigen) - whether it originates from the disease agent or the immune component - the B cells with the most suitable antibodies for the specific threat are transferred to designated "training sites" within the lymph nodes (lymph nodes). Within these niches, the cells go through division cycles and genetic changes, thus polishing their ability to produce antibodies with a high affinity to the threat. The "polished" B cells remain in the body, giving it long-term immunity.

Besides these "training programs", the lymphatic organs in the intestines have another important role: control of the intestinal bacteria. This multiplicity of roles makes it difficult for researchers to examine each of the tasks of the lymphatic organs in the intestine separately. In addition, the training sites in the intestinal organs are too small and hidden to be able to observe them with conventional imaging methods. To deal with these difficulties, Dr. Ziv Shulman and research student Adi Biram from the Institute's Department of Immunology developed a method that makes it possible to isolate the lymphatic organs in the intestine and perform their imaging using an equivalent of the "transparent brain" method in neurobiology. As the name suggests, with this method the tissue becomes transparent - except for specific cells that you want to study. Using this method, the researchers were able to see with a special fluorescent microscope that allows imaging of whole organs, what is happening at the training sites in an entire lymphatic organ in the intestine. To this end, the researchers injected mice with a vaccine orally and examined the immune response that took place in their digestive system.

"We discovered that the lymphatic organs in the intestine operate according to a different set of rules than the one that characterizes the peripheral lymphatic system," says Dr. Shulman. In fact, the lymphatic system in the intestine does not collect antigens through tissue drainage, as the peripheral lymph nodes do, but by active absorption of the vaccine particles or the pathogen from the intestine. Also, unlike the peripheral system, which is a "capitalist" system by nature, i.e. aimed at creating the most effective antibodies at the highest speed, the lymphatic system in the intestine supposedly operates according to a more "socialist" principle, at least in the first stage: it first allows all the B cells divide and secrete antibodies in response to a threat regardless of their affinity for the antigen. However, later on, the cells that produce antibodies with a higher affinity will be "accepted" to the training sites for allocation of improvements.

In the next step, the researchers used the method they developed to observe the "trainer" cells that select the B cells with the highest affinity. They discovered that unlike the peripheral lymphatic system, the "training" cells in the intestine were unable to distinguish between high-affinity and low-affinity antibodies. This limitation, the researchers believed, stems from the complexity of the environment in which the lymphatic organs in the intestine operate: they are exposed to huge amounts of antigens that originate from bacteria residing in the intestine on a regular basis. Under these conditions, the antigens of the vaccine "disappear in the crowd" - diluted to such an extent that it is impossible to select B cells based on their affinity to them. In accordance with this hypothesis, when the researchers artificially increased the antigen levels in the intestines of the mice, they were able to make the "trainers" select the most competent B cells.

Understanding the unique activity of the immune system in the gut is an important step towards expanding the use of orally administered vaccines. Thanks to the ease of use of oral vaccines, their greater availability will likely allow for increased vaccination rates among different populations. In addition, as mentioned, thanks to the route in the body of these vaccines, they may provide better protection against many pathogens that enter the body through mucous tissues in the intestine, nose, mouth and genitals.

One response

  1. Interesting, but not really new. For some diseases in which the infection passes through the mucous tissues, such as polio and typhus, there are now vaccines given orally or by injection. In both cases it is known that the oral vaccine is much more effective than the injection vaccine. On the other hand, for diseases that are transmitted by injection by mosquitoes, such as malaria, yellow fever, etc., there is no oral vaccine. Even if such a vaccine is developed, it will probably always be better to vaccinate by injection.
    By and large, the introduction of the commercial-marketing interest in the articles does not add interest to those interested in science. And it's also too speculative, you won't see it in the scientific article. I should have written an article about the research innovations and left all the BS (bol-shit in Hebrew: Shit of Priim).

Leave a Reply

Email will not be published. Required fields are marked *

This site uses Akismat to prevent spam messages. Click here to learn how your response data is processed.