Just one dose of a new nanoparticle-based COVID-19 vaccine is enough to generate an immune response in animals, and the vaccines currently in clinical use are on track. With minor changes, Northwestern University researchers hope the same vaccine platform could target other infectious diseases.
In a new study, mice that received protein-based immunizations survived 100% when challenged with a lethal dose of the SARS-CoV-2 virus, which causes COVID-19. None of the mice developed lung damage due to SARS-CoV-2 exposure. All mice that did not receive the nanoparticle vaccine died during the 14-day trial.
The findings, published this week in the Proceedings of the National Academy of Sciences, outline the structure-function relationship between the first spherical nucleic acid (SNA) vaccine developed to prevent viral infection.
The nanoparticles, known as SNAs, house immune targets, globular DNA that can enter and stimulate immune cells with extremely high efficiency. SNAs have been tested in more than 60 cell types. The researchers experimentally determined the ideal ratio between the SNA's shell and core densities that would yield the most efficient response.
The SNA vaccine has already been used to treat mice with triple-negative breast cancer—more vaccines for other cancers are in development.
"This is a striking demonstration of rational vaccinology -- that a vaccine's structure, not just its components, can have a profound effect on efficacy," Mirkin said. "While we have previously shown that this is the case for cancer immunotherapy, this is the first demonstration of an infectious disease.
Making the drug
Vaccines often take years to develop. But with COVID-19 there has been amazing progress in the field. Mirkin challenged Teplensky, a postdoc in Mirkin's lab, to work alongside Ph.D. student and co-first author Max Distler, assessing whether the SNA platform could be used to create a potent vaccine and expand its reach. The two completed the project in just nine months.
Typical viral immunity consists of a mixture of molecules from the virus (called antigens) that tell the immune system what its target will be (the virus), and other molecules (called adjuvants) stimulate the immune system to enhance the body's response to tackle that target when it appears later.
Mirkin coined the term "rational vaccinology" to describe how the co-administration and timing of these two drugs through a single nanoparticle could make a vaccine more effective. Small changes at the nanoscale can have a major impact on the efficacy and predictability of vaccines.
Mirkin's team packaged antigens (parts from COVID-19's spike protein) within the core of the SNA and used specific DNA sequences (adjuvants) known to stimulate the immune system as a radial shell around the core. The researchers injected mice subcutaneously to elicit an immune response to the spike protein, then monitored antibody production for several weeks after the injection.
Challenging the results
Two weeks after injection, mice vaccinated with SNA produced the highest antibodies compared to mice vaccinated with a simple saline mixture of the same composition, even better than other formulations 14-fold increase in commercial use of adjuvants (already used in formulations for shingles, hepatitis B and influenza vaccines).
Antibodies are associated with preventing infection, establishing the potential of this platform in the field of COVID-19 and infectious diseases. Protein-based vaccines also have fewer side effects and can be stored at normal refrigerator temperatures, greatly reducing production and distribution costs.
Stopping future viruses
Using COVID-19 as a case study to compare how well the vaccine worked was mainly practical. But it also calls attention to the broader implications of the SNA as an infectious disease platform.
Teplensky says that COVID-19 caused a shift in behavior toward infectious diseases. "People didn't recognize and appreciate the emergent power that infectious disease can have," Teplensky said. "We saw an opportunity to use COVID as a case study to shed light on the shortcomings in the vaccination space."
Distler said, "with this case study, although the results are quite impressive, the goal was not to compete with existing COVID vaccines. We're preparing for the next mutation, or the next disease in need of a highly structured vaccine because eventually there will be another emergent disease." According to the researchers, the platform could even be used to target something as complex as HIV.
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