The scientists of the Weizmann Institute of Science have discovered antibody-producing cells in the bone tissue of the nasal concha and thereby plant hope for the development of more effective nasal vaccines and new treatments for allergies and neurological and autoimmune diseases
The nose is a gateway to our body - to air, smells and also to pathogens. On its way in, the air we breathe flows through the nasal turbinates (turbinates) - elongated bony shelves that protrude from the nasal wall and roll inward like shells. The shells are coated with a unique tissue that secretes mucus (snot), they contain many extensions of nerve cells responsible for the sense of smell, and their structure allows the air to warm up and absorb moisture before it reaches the lungs. But the shells that stand at the entrance to the body also have a weak point: due to their proximity to the brain, they are not accessible to the immune system's antibodies through the bloodstream. So how do we still enjoy relative protection and not get sick all the time? In a new study, whose surprising findings are published today in the scientific journal Nature, Weizmann Institute of Science scientists revealed that antibody-secreting cells migrate into the nasal concha during illness or after receiving a vaccine and secrete antibodies from the concha into the nasal cavity. The discovered cells open a window to effective nasal vaccines and new treatments for allergies and neurological and autoimmune diseases.
In the days when the corona spread rapidly as a global epidemic, millions around the world followed closely the reports of progress in the development of innovative corona vaccines that can be given by nasal spray instead of injection. Although this idea has not succeeded yet, it was not fictional at all: there are currently vaccines, including the flu vaccine, that are administered through a nasal spray that contains live, weakened viruses. However, no single vaccine dose is effective on its own, and these vaccines are given as a first dose and then a booster dose. To date, the mechanism of action of nasal vaccines and the reason for the need for booster doses have not been fully understood.
check the immune response without damaging the organs of the immune system
In an attempt to shed light on the issue, Prof. Ziv Shulman from the Department of Systemic Immunology at the Institute, to examine how organs of the immune system in the nose and pharynx area react to nasal vaccines. To this end, the researchers, led by Jingying Liu from Prof. Shulman's laboratory, used imaging methods that allow monitoring the immune response without damaging the organs of the immune system; In humans, these organs include the tonsils and the adenoid ("third tonsil") called the lymphatic belt after Valdier.
The scientists discovered that in mice that received a dose of vaccine through the nose, a targeted immune response arose from B cells - the antibody producers of the immune system. These cells, located near the mucous tissue covering the nasal cavity, recognized the immune molecules and began to rapidly divide and differentiate. This differentiation process is a sort of biological "specialization program" that will eventually turn into cells that secrete specific antibodies to the disease agent or into memory cells that are preserved over time in case of future infection.
Those who help the B cells to pass the specialization program, and even participate in the selection of the cells that will survive in the end, are T cells of a certain type, but the scientists discovered that the number of these in the immune organs in the nasal area is not sufficient to create an effective immune response. "The need for a massive migration of T cells to the area explains why vaccines are not even effective after the first dose and require a booster dose," explains Prof. Shulman. "Only after the second dose are enough T cells formed that are required to transform B cells into effective antibody secreters and memory cells." The scientists estimate that the lack of T cells is intended to prevent hypersensitivity to foreign factors that are carried in the air in harmless amounts. "It is possible that this mechanism goes wrong in allergies and various autoimmune diseases, and therefore understanding it may open a window to new treatments for these conditions," adds Prof. Shulman.
look for the immune cache
The discovery of the immune mechanism that is activated in response to antibodies was only the starting point for a frantic search for the target where the antibody secretors that have completed the differentiation process are located. "To our surprise, we found the B cells in the turbinates themselves - a bone tissue that was not known as a niche that supports an antibody-mediated immune response," Prof. Shulman describes the unusual findings. "The location of the cells in the bones is similar to what happens in the bone marrow, and it is possible that this niche has additional functions besides the immune mechanism we identified."
According to the new findings, the cells that secrete the antibodies settle near the glands that secrete mucus in the nasal shells, just below their outer layer of cells, and that they secrete their antibodies into the glands. This immune protection bridges the lack of ability of antibodies to reach this entry gate through the bloodstream, and is important not only in the context of viral and other diseases, but is a protection for the brain and the many nerve branches that reach the area and are responsible for a functioning sense of smell.
"There is a nose-brain barrier and these immune cells stand as guards at the gate," says Prof. Shulman. "I hope that it will be possible to use their access to the olfactory nerves in order to design vaccines for neurological diseases. The potential is great since these diseases are sometimes caused by the accumulation of damaged proteins in the brain and the formation of deposits. Many research groups are focusing on the possibility of treating them with antibodies that will bind and neutralize those harmful proteins. Our research reveals an entry point to a fortified target - antibody-secreting cells with access to the central nervous system."
Dr. Liat Stoller-Barak, Dr. Hadas Hatzroni-Baravi and Dr. Adi Biram from the Department of Systemic Immunology at the Institute also participated in the study; Sasha Levon, Dr. Natalia Davidson and Dr. Moshe Biton from the Department of Immunology and Biological Regeneration at the Institute; Dr. Mirav Kadami, Muriel Shemla, Dr. David Piltzer from the Department of Life Sciences Research Infrastructures and the Israeli National Center for Personalized Medicine named after Nancy and Steven Grand at the institute; Dr. Marina Cohen and Dr. Uri Brenner from the department of veterinary resources at the institute.
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