New vaccine concept against Sars-CoV-2 successfully tested
23.05.2023 17:01
Researchers at the University of Basel have developed a new approach for a vaccine against Covid-19. The vaccine is based on modified coronaviruses that penetrate cells and trigger an efficient immune response, but cannot multiply in the body. In animal experiments, the vaccine effectively protected against the disease and even prevented virus transmission. Clinical studies on humans are expected to follow soon.
Although safe and effective Covid-19 vaccines have been available since the beginning of 2021, Sars-CoV-2 continues to spread and is constantly producing new variants. In some regions the population lacks access to vaccines, in others there is a lack of trust in the new mRNA vaccines. New vaccines that are easy to store and administer and provide efficient immune protection would be an important step in keeping the coronavirus at bay in the long term.
Researchers led by Prof. Dr. Thomas Klimkait from the Department of Biomedicine at the University of Basel, together with the company RocketVax, are now presenting a vaccine concept that could produce a new generation of vaccines against Sars-CoV-2. The concept can also be quickly adapted to new variants and other viruses. Their promising results will now be submitted to a specialist journal for independent review and publication and are accessible on a preprint server.
Viruses that are unable to reproduce
“1-cycle viruses” is how the researchers describe the principle of their novel vaccine. The vaccine is based on a specially adapted version of the virus that can be reproduced in the laboratory. However, the 1-cycle viruses cannot multiply further in body cells after their initial penetration.
A virus normally contains the blueprints for all the components required for new virus particles in its genome. Once in a body cell, the virus then abuses the cell machinery: the cell begins to replicate the virus. The newly built viruses then destroy the cell and infect other cells.
For their vaccine, however, the researchers are modifying the virus genetic material: “Among other things, we are removing a specific gene from the blueprint for the virus envelope,” explains virologist Klimkait. If this envelope component is missing, no new virus particles can be created. However, the individual parts of the virus are produced. The body cell presents this on its surface to the immune system, which recognizes the virus building blocks and builds up effective immune protection.
Vaccine production with a special cell line
In order to multiply these viruses, which can no longer reproduce in body cells, for vaccine production, the researchers developed a so-called production cell line. To do this, they incorporated the missing gene for the virus building block into the genome of cells in the laboratory, so that they can permanently produce this building block. If the team now introduces the modified virus genetic material (with an incomplete blueprint for the virus shell) into the production cells, they build new virus particles.
“Outwardly, these vaccine viruses are completely identical to the normal coronaviruses. But the virus envelope gene is missing from their genome. This means that they cannot reproduce in normal body cells that have no substitute,” says Dr. Christian Mittelholzer, scientist responsible for the project.
Improved immune response
Aside from the missing blueprint for the virus shell building block, the researchers changed other details of the virus genome: They removed genes that allow the virus to inhibit the cell's defense reaction. These changes are aimed at enabling the most effective immune response to the virus and building strong and longer-lasting immune protection.
The researchers recently successfully tested their new vaccine on hamsters: After immunization administered via nasal drops, 20 out of 20 animals were protected: They did not develop any symptoms even after contact with a high dose of the natural Sars-CoV-2. In addition, the vaccination could prevent other, unvaccinated animals from becoming infected; According to current knowledge, they built up sterile immunity.
Vaccination without a needle
The vaccine should also be administered to humans via the nose or mouth. Since the 1-cycle viruses are very stable, the vaccine can easily be stored in the refrigerator for a long time, confirms Klimkait. The research team is now planning production and an initial study with a small cohort of test subjects in Switzerland.
If new variants or even a “Sars-CoV-3” emerge, a suitable vaccine could be produced very quickly using the same concept, says Klimkait.
“Technically speaking, we bring the modified viral genome into the production cell line in several individual pieces because such pieces are easier to produce and introduce.” Inside the cell, repair enzymes ensure that the individual pieces of the virus genome become a whole again. “This also means that, for example, we can easily replace the section with the blueprint for the spike protein if a new variant with new mutations emerges.”
No reconversion of the vaccine viruses is possible
Klimkait emphasizes that it is impossible for the missing gene for the virus envelope component to come back. “The coat protein gene is located in the genome in the nucleus of the production cell. The viral genome, on the other hand, always remains outside the cell nucleus - so they never meet, and the viral genome cannot revert to the original version.
The researchers led by Thomas Klimkait and Christian Mittelholzer have applied for a patent for the system. The development and preclinical studies of the new vaccine took place in collaboration with the company RocketVax and, for animal experiments, with the Friedrich Loeffler Institute in Germany. The collaboration is embedded in a research collaboration with the University Hospital of Basel and the Swiss Tropical and Public Health Institute (Swiss TPH). The University Hospital of Basel and the canton of Basel-Stadt provided start-up financing for the preclinical research work on the new vaccine that has already begun. The project also received financial support from Innosuisse.