Under the background of the global COVID-19 pandemic, amazing progress has been made in the field of vaccine research and development, and there are more and more different types of vaccines based on different principles. Recently, the Chad Mirkin team of Northwestern University published a research paper entitled Sphericalnucleic acids as an infectious disease vaccine platform in the Proceedings of the National Academy of Sciences (PNAS). In this study, spherical nucleic acid (SNA) was applied to the development of COVID-19 vaccine. In animal trials, a single dose of SNA nano-vaccine is enough to protect SARS-CoV-2 from infection.
More importantly, this SNA nano-vaccine can not only be used to fight against COVID-19 pandemic, but also can be extended to other infectious diseases, and even other new infectious diseases that may break out in the future.
Unlike previous vaccine development, which focused on the selection of immunogens or the activation of adjuvants, the development of SNA vaccines paid more attention to whether the vaccine components could be perfectly presented to the immune system.
Introduction to SNA
The SNA used in this study, developed by Professor Chad Mirkin, is an SNA nanoparticles formed by connecting nucleic acids (DNA or RNA) to the surface of nanoparticles, which can efficiently enter the body and quickly stimulate the immune system. SNA has previously been tested in more than 60 cell types and vaccines, and has been designed as a vaccine strategy for a variety of diseases.
The team developed an experimental SNA drug, which has been shown to penetrate the blood-brain barrier, inhibit the expression of oncogenes, and trigger tumor cell death in clinical trials of fatal glioblastoma. The result of this study is of great significance. It is the first time that nanotherapy agents have penetrated the blood-brain barrier through intravenous infusion and changed the genetic mechanism of tumors to cause tumor cell death.
In addition, SNA vaccines for triple-negative breast cancer have been preclinical validated, and more vaccines of this type for other cancers are being developed.
R&D of SNA COVID-19 Vaccine
The classic viral immune process requires a viral antigen, which tells the immune system what the target is, to stimulate the immune system and improve the immune effect of the antigen. However, how to present these two components to immune cells in an appropriate proportion is still a very thorny problem.
The integration of antigens and adjuvants into a structural support may be the key to solving this problem. In the study of SNA COVID-19 vaccine, the research team wrapped SARS-CoV-2 receptor binding domain (RBD) in the liposome core and attached it to the liposome core using TLR9 agonist CpG oligonucleic acid as an immune adjuvant, which stimulates the immune system.
The team injected the uniquely designed SNA COVID-19 vaccine into mice to induce an immune response to spike protein on SARS-CoV-2, and then monitored the production of antibodies within a few weeks after injection. Two weeks after injection, mice vaccinated with SNA vaccines produced higher titers of antibodies than mice vaccinated with a simple saline mixture of the same ingredient, and the antibody level is even 14 times higher than other formulations containing commercial adjuvants (already used for herpes zoster, hepatitis B, and influenza vaccines).
Not only that, the research team also sent their vaccine to the Argonne National Laboratory (ANL) in the United States for live animal infection tests of SARS-CoV-2. The double-blind study showed that mice injected with SNA vaccine survived until the end of the trial with the infection of a high dose of SARS-CoV-2, and there was no lung injury caused by COVID-19. By contrast, all the mice that did not receive the SNA vaccine died during the 14-day trial.
These animal test data confirm the great potential of SNA platform in the field of COVID-19 and infectious diseases. In addition, SNA vaccine has the advantages of low side effects and easy store with ordinary refrigerators, which greatly reduces the costs of production, transportation, and distribution.
Professor Chad Mirkin says the study confirms the importance of vaccine structure, which can have a profound impact on vaccine efficacy. In fact, this is also a completely new attempt. Although the team has previously proved that SNA vaccine can treat and prevent cancer, it is the first time to apply it to infectious diseases such as COVID-19. Their goal is not to compete with the existing COVID-19 vaccine, but to prepare for the next infectious disease that requires a highly structured vaccine. The modularization of the SNA vaccine research and development platform means that once a new infectious disease emerges, it may only need to change antigens or adjuvants to respond quickly to future viruses.