New platform
Nanovaccine against covid and those who will be after it
Researchers from Northwestern University (Northwestern University, Evanston, USA) report that the spherical nucleic acid vaccine they developed completely protected a group of vaccinated mice from covid. The lethal (tested on a control group of animals that completely died for the sake of science) dose of SARS-CoV-2 was defeated by immunity that arose after the introduction of a new vaccine. But the task of scientists is not just to create another anti—virus agent, but to build a technological base to combat still unknown threats: it is obvious that humanity is not the last time faced with new evolving viruses.
Details are disclosed in a scientific article published in the Proceedings of the National Academy of Sciences (Teplensky et al., Spherical nucleic acids as an infectious disease vaccine platform).
"What distinguishes our vaccine from other vaccines is the approach we use to develop it," says the doctor Michelle Teplensky, the first author of the publication in PNAS. "A few years ago, people focused on choosing the right target for training the immune system and the right stimulator to activate it, but not on how these components should be organized structurally and presented to the body."
Nanostructures known as SNAs, Spherical Nucleic Acids, spherical nucleic acids, due to their shape, penetrate immune cells especially effectively. In the laboratories of Northwestern University, the ideal ratio between the density of the shell and the nucleus of spherical nucleic acid, which gives the most powerful immune response, has been experimentally determined.
Nucleic acid can form a conditionally spherical structure.
Experiments with SNAs have been conducted since the beginning of the XXI century. Animal models have shown the effectiveness of these structures in the treatment of several types of cancer. The head of the study, Professor Chad A. Mirkin (Chad Alexander Mirkin, the most cited nanochemist of the last two decades, SNAs were created and developed under his leadership) is confident that preparations based on spherical nucleic acid can be effective in fighting infections.
"This is a wonderful demonstration of rational vaccinology — the idea is that the structure of a vaccine, not just its components, can have a profound effect on effectiveness," Mirkin notes. "We have previously shown that this applies to cancer immunotherapy, and now for the first time we have demonstrated that it also works in the case of an infectious disease."
Previously, vaccines were developed for years and decades. But COVID-19 made it work faster. For this project, Mirkin formed a very small scientific group — its core was Teplensky (a postdoctoral fellow in Mirkin's laboratory) and a doctoral student Max Distler (Max E. Distler). The young scientists were faced with the task of evaluating the prospects of SNA as a platform for creating a powerful vaccine. They completed the work in just nine months — about the same time that it now takes some commercial developers to develop a vaccine.
A typical antiviral vaccine is a mixture of virus molecules (so—called antigens) that tell the immune system what its target (the virus) will be, with other molecules (so-called adjuvants) that stimulate the immune system. Since it is a mixture of individual molecules unrelated to each other, not all immune cells of patients receive a sufficient dose of both antigens and adjuvants.
That's where the structure is needed. Mirkin introduces the term "rational vaccinology" to show how joint delivery and time of reception of two components through one nanoparticle can make vaccines more effective. Tiny changes at the nanoscale promise big implications for vaccine effectiveness and predictability.
How does a nanovaccine work? The antigen (part of the infamous COVID-19 spike protein) is packed in the SNA nucleus; and a specific DNA sequence, which is known to stimulate the immune system (adjuvant), acts as a radial envelope surrounding the nucleus. The researchers injected the drug into mice under the skin, triggering an immune response to the spike protein, and then monitored the production of antibodies for several weeks after injection. It turned out that such a vaccine causes an order of magnitude stronger immune response than a simple mixture of active ingredients.
Max Distler noted: "In this study, although the results are quite impressive, there was no goal to compete with existing covid vaccines. We are preparing for the next mutation or the next disease that needs a highly structured vaccine, because there will definitely be another disease in the future."
According to the researchers, the approach can also be applied to combat intractable diseases, such as HIV/AIDS.
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