If the immune protection built up does not effectively prevent further corona infections, it has always been said that this is due to the spread of new virus variants. This is not the only cause.
The mRNA vaccines against Sars-CoV-2 have saved millions of lives because they protect against serious illnesses. But long-lasting protection against further infections was not achieved.
Lindsey Wasson / Reuters
New corona variants are constantly emerging. And each one leads to another infection. But why do neither vaccinations nor previous infections provide robust protection against further infection? New studies provide evidence that, in addition to the genetic changes in the virus, its surface and the way the vaccine works are the reasons why we are not better prepared for the next cold season.
Long-lasting memory cells are missing
When a pathogen enters our body, the immune system quickly and extensively multiplies the immune cells that produce specific antibodies against the respective invader. These cells are called B cells. Production is started even after a corona infection or vaccination. These antibodies then neutralize viruses floating around in the body.
To ensure that we do not constantly become ill with the same pathogen, another protective mechanism has developed over the course of evolution. After an infection, long-lasting memory cells are formed. If a virus enters our body for the second time, a specific defense force is already ready.
The memory cells, which produce antibodies specifically directed against a pathogen, retreat into a cozy nest in the bone marrow. Here they are supplied with nutrients and can even survive for several decades. They continually produce a small amount of antibodies.
But these long-lasting antibody memory cells apparently do not form after a corona infection or after a vaccination with an mRNA vaccine. This is shown by analyzes of the bone marrow of people after one or more infections or vaccinations.
Since suctioning bone marrow is a painful procedure, such examinations have so far only been able to be carried out on a few test subjects. The team led by Mohammad Sajadi from the University of Maryland in Baltimore analyzed the bone marrow of 20 unvaccinated people after a corona infection. The research group Eun-Hyung Lee from Emory University in Atlanta carried out these studies on 19 people after multiple vaccinations with an mRNA vaccine.
The database is still small. But the results of the two teams correspond well. And they provide a valid explanation why specific antibodies can only be detected in the blood for a few months after both a corona infection and an mRNA vaccination: The supply is missing because there are no long-lasting memory cells in the bone marrow.
The problem is the arrangement of the spike proteins
For immunologist Martin Bachmann from the University of Bern, the structure of the coronavirus and the way the mRNA vaccine works is the reason for the deficiency. The authors of the bone marrow analyzes mentioned also see it that way.
“In order for long-lasting antibody-producing cells to emerge, a relatively immature B cell must receive a specific signal,” explains Bachmann in an interview. Each B cell has special antennas on its surface. Only if 10 to 15 of these antennas can dock onto proteins on the same virus or vaccine particle at the same time will the maturation signal be triggered.
But for this to happen, the docking stations have to be arranged very closely, namely only 5 to 10 nanometers apart. This is also the case with influenza and many other viruses. Their proteins protruding from the virus particle are so close together. The situation is different with Sars-CoV-2: the viruses’ spines are arranged a little more loosely and are 25 nanometers apart.
There are no surface structures at all on the particles of the mRNA vaccine. The particles serve to ensure that the virus mRNA gets into a body cell, where the spike proteins of the virus are produced and then presented on the surface. But after an mRNA vaccination, the docking stations on the cells are approximately 50 nanometers away, says Bachmann.
Sars-CoV-2 is, so to speak, doubly clever – from its perspective. It is constantly changing, and its structure prevents the formation of long-lived B cells. There is evidence that the well-known coronaviruses that have been plaguing us with regular colds for decades, if not centuries, have a similar structure to Sars-CoV-2 and therefore cannot produce long-lived B cells.
Do mRNA vaccines have a general deficit?
If we wanted to get long-lasting protection against infection with Sars-CoV-2, we would have to develop new vaccines. In most cases, a corona infection is no longer a serious illness. But on the one hand there is the danger of Long Covid, on the other hand the constant absences of employees are causing economic losses and bottlenecks in important sectors such as the healthcare system.
Various examples show that vaccines can in principle provide long-lasting immune protection: protection against measles or smallpox viruses lasts for decades, while protection against tetanus or the same influenza variant usually lasts for a few years. This fits with the findings from the new studies. Long-lived B cells that produce antibodies against influenza viruses or tetanus toxin were found in the bone marrow.
Apparently all of these vaccines have the right structure: the docking stations for the B cell antennas are close enough together. This is a coincidence, because when these very old vaccines were produced, no one knew that this was important. These vaccines are inactivated viruses or virus-like protein structures.
The question now arises as to whether the formation of the important long-lived B cells is generally not possible with mRNA vaccines or only in the case of Sars-CoV-2. As long as this is not clarified, Bachmann does not think it is a good idea to replace proven vaccines with mRNA products.
However, the mRNA vaccines used still provide good and lasting protection against severe Covid disease. It is not the long-lived B cells that are responsible for this, but rather a different type of cell: immune cells that destroy infected cells and their invaders. And they are activated very well by the mRNA vaccines.
