A new vaccine against COVID-19 based on modified mesenchymal stem cells has been tested successfully

Chinese researchers have proposed a new approach to the development of a vaccine against coronavirus infection (COVID-19), based on human mesenchymal stem cells, with a positive and promising antibody response.

Scientists around the world are working at an unprecedented pace to find a vaccine against the severe acute respiratory syndrome (SARS) caused by the SARS-CoV-2 coronavirus, the causative agent of the COVID-19 pandemic. Despite the fact that at present there are several developments that occupy a leadership position in creating a potential vaccine, there is still a long way to go to get the medication ready for use.

Such a large-scale positive shift was facilitated by a detailed molecular study of SARS-CoV-2 since the start of the pandemic. Today it is known that one of the components of the virus, a structural nucleocapsid protein (N-protein), can cause the development of a stable protective immune response.

However, the main weaknesses of current potential vaccines are low levels of efficacy, immune adaptability, tolerability and safety. In addition, most vaccines do not manage with the modifications that arises in the host during replication of the virus. All this means that the preclinical search for promising candidates for the role of the vaccine is still far from complete.

In a recent revolutionary article published in bioRxiv, Chinese researchers Junhua Liu, Huping Jiao, and Xiushan Yin demonstrated that modified mesenchymal stem cells expressing SARS-CoV-2 proteins can be used as a new and effective platform for vaccine production.

Transfection of mesenchymal stem cells with N-protein

In their experiment, scientists used allogeneic mesenchymal stem cells (MSCs) obtained from human umbilical cord, which are usually used in cell therapy for transplantation. MSCs were evaluated by flow cytometry analysis and functional assay.

After four passages, primary mesenchymal stem cells were transfected with a plasmid expressing the N-protein. The average transfection efficiency after 48 hours was 20%.

The resulting mesenchymal-SARS-CoV-2-N cells were used for injection into mice. A total of 1 million modified MSCs were inoculated in mice either intramuscularly or subcutaneously to produce vaccine antigens in vivo. At the same time, 5-8 mice were randomly selected from the same group before injection to use their sera as a negative control.

Blood samples were taken from mice 20 days after vaccination. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the ability to produce antibodies against N-protein.

Reliable method for producing antibodies against SARS-CoV-2

The results showed that after 20 days almost all immunized mice in the serum had developed antibodies, and at least half of them after a single intramuscular or subcutaneous dose of the cells showed active positive expression of antibodies.

The reaction after these two types of injections showed similar efficacy. In addition, mice that were given a test injection with a control (blank) vector did not show anti-N protein antibody production, and the ELISA was comparable to mice that were not injected with anything. Although the potential risk of any cell vaccine is that residual cells present in the body might cause uncontrolled proliferation and malignancy, the authors of the study also claim that the mesenchymal stem cells were disposed of by the immune system 20 days after the injection.

Promising COVID-19 prevention approach

In any case, a practical stem cell-based research route (described in this article) may allow several antigenic proteins to be presented as targets using the secretion feature of part of the SARS-CoV-2 antigenic protein.

Even more important, some of the SARS-CoV-2 proteins, mediated and secreted by stem cells, may be modified with acetylation and glycosylation processes, imitating the virus protein variation in vivo. This, turnabout, can mimic the reaction and significantly increase the success of establishing adequate immune defense.

“Combined with the advantages of mesenchymal stem cells in the treatment of diseases, we believe that such stem cells or cell-based vaccines will be a promising strategy to control COVID-19 and other coronaviruses with unknown potential risk, and it is also a promising model for some pandemic diseases”, – conclude study authors.