Outline of the Lecture on the Novel mRNA Vaccines


"What are the differences between novel coronavirus vaccines and conventional vaccines? ~ Need-to-know things about RNA vaccines ~."

The 29th Annual Meeting of International Congress on Nutrition and Integrative Medicine (ICNIM2021) was held online on July 10, 2021. Dr. Yoshiharu Matsuura, director of the Center for Infectious Disease Education and Research, Osaka University, presented a lecture at the public symposium. The outline of this lecture is as follows.

History of infectious diseases and SARS-CoV-2
A variety of microorganisms, such as bacteria and viruses, live in the environment and organisms, coexisting with us. Actually, only a small number of such coexisting microorganisms have pathogenicity to human, and they are responsible for infectious diseases which humanity has been fighting against repeatedly since ancient times. In the long history of the fight, SARS-CoV-2, the virus responsible for the novel coronavirus infection (COVID-19) has been found to have the largest genome among the viruses that have RNAs as their genetic information. Generally, it is essential for viruses to enter living cells in order to propagate. In SARS-CoV-2 infection, the spike proteins of the virus that bind to the cell-surface ACE2 receptors on the host side were shown to be critical points for vaccine development.

The World First Gene-based Vaccine
The SARS-CoV-2 vaccine is the world first gene-based vaccine mainly composed of messenger RNA (mRNA; protein-blueprint) that produces viral spike proteins in the body of the host. When the spike proteins are produced by mRNA contained in the vaccine, the host recognizes them as foreign substances and produces specific antibodies. The mechanism of the SARS-CoV-2 vaccines are distinct from conventional vaccines which contain inactivated or attenuated viruses or include part of the structural proteins of the virus. Since the use of mRNA as vaccine is a revolutionary solution and its vaccine effect is highly evaluated, high expectations are growing. In addition, basic research such as producing the modified SARS-CoV-2 which can infect the mouse has been developed. The vaccine development engaged by Osaka University was also introduced.

Viruses and mutations
Dr. Matsuura commented on SARS-CoV-2 variants of recent concern. It is known that RNA viruses including SARS-CoV-2,are inherently easy to have mutations because RNA virus replication is much less accurate than DNA virus replication. On the other hand, they are replicating at a threshold level that does not fall outside the environmental fitness, because too many mutations lead to the loss of important information of the viral body and they become unable to survive as a population.  Dr. Matsuura said that “Probably SARS-CoV-2 is now looking for the level where it can continue to exist."

Progress of Covid-19 symptoms and immune reactions after infection
In the mild cases of SARS-CoV-2, the innate immune system acts in the early stage of infection. Then the acquired immune system, represented by T cells and B cells, works to produce antibodies, which also exert cytotoxic activity of T cells, and the virus quantity turns down to recovery. However, when severe cases are observed, the rise of the acquired immune system is slow. It becomes difficult to suppress the virus because the activity of T cells is weak even if the antibodies are produced, resulting in severe condition. In addition, a report published in the scientific journal Cell (2020) suggested that the activation of immune cells, such as helper T cells and killer T cells, rather than antibody levels, is a factor that reduces the severity of the disease. Taking these into account, Dr. Matsuura stressed the importance of maintaining the cell-mediated immunity represented by acquired immune system on a regular basis, although the antibody titer by the vaccine tends to be too much focused.

Knowing Viruses Correctly
At the end of the lecture, Dr. Matsuura appealed for the importance of knowing viruses correctly to coexist with them: "Although there are always trillions of viruses in an organism, it is only a handful of viruses which show pathogenicity to us. Since those viruses know the cells better than humans, we should know the viruses and live well with them."