Future Infectious Diseases: A Nanoparticle-Based Vaccine

Future Infectious Diseases: A Nanoparticle-Based Vaccine ...

Only one dose of a new nanoparticle-based COVID-19 vaccine was sufficient to produce an immune response in animals on track with vaccines currently being used in clinical use. And, with minor modifications, Northwestern University researchers hope the same vaccination platform will target other infectious diseases.

100% of mice who received the protein-based immunization were given lethal doses of the SARS-CoV-2 virus, which causes COVID-19. None of the mice was suffering lung damage due to the SARS-CoV-2 exposure. All mice who did not receive this nanoparticle vaccine died in a 14-day study.

These findings, published this weekin theProceedings of the National Academy of Sciences, outline the structure-function relationships between the first spherical nucleic acid (SNA) vaccination to protect against viral infections.

What makes this vaccine different from other vaccinations is the approach we take to develop them, according to Dr. Michelle Teplensky, the first author of the paper. Even as recent as a few years ago people focused on selecting the right target to train the immune system and the right stimulant to activate it, not on how these components were arranged structurally and presented to the body.

The nanoparticles that house the immune target are a form of globular DNA that can enter and stimulate immune cells with great efficiency. SNAs have been tested in over 60 cell types. Researchers studied the ideal ratio between the SNAs shell and core density that produces the most powerful response.

SNA vaccinations have been used to treat mice with triple negative breast cancer, and more vaccinations for other cancers are in development.

Chad A. Mirkin, the inventor of SNAs and the author of the papers, conducted the study and said the platform may lead to infectious diseases.

This is a remarkable demonstration of rational vaccinology the idea that the structure of a vaccine, rather than just components, can have an effective effect, according to Mirkin. Although this has previously been shown to be the case for cancer immunotherapies, this is the first demonstration for an infectious disease.

Mirkin is the George B. Rathmann Professor of Chemistry at Northwestern University, director of the International Institute of Nanotechnology, and a member of theRobert H. Lurie Comprehensive Cancer Center of Northwestern University.

Making the drug

COVID-19 is usually a year''s long process, but Mirkin challenged Teplensky, a postdoctoral researcher, to collaborate on the SNA platform to develop a powerful vaccine and expand its potential impact in nine months.

Typical viral immunizations are made up 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) to stimulate the immune system when it appears later. However, researchers believe that cells within patients aren''t receiving a significant dosage of both antigens and adjuvants.

Thats where structure comes into play. Mirkin used the term rational vaccinology to describe how co-delivery and timing of these two drugs via one nanoparticle can make vaccines more effective. Tiny changes at the nanoscale may have significant implications for a vaccine''s efficacy and predictability.

The Mirkins team hid the antigen (a portion from the COVID-19s famous spike protein) inside the core of an SNA, and used a specific sequence of DNA known to stimulate the immune system (adjuvant) as the radial shell surrounding the core. In the weeks following injection, the researchers investigated the immune response to the spike protein.

Challenging the results

mice vaccinated with the SNA vaccine had the highest antibody production, up from those vaccinated with a simple saline mixture of the same components, although other techniques have been reduced by 14 percent.

Antibodies are linked to protecting against infection, establishing the platforms possibilities in the COVID-19 and infectious disease space. Protein-based vaccinations also have less side effects and can be stored at normal refrigerator temperature, thus lowering production and distribution costs significantly.

Researchers examined commercially available COVID-19 vaccination papers and found that other studies completed antibody production at least two weeks ago was on track.

In a double-blind analysis, the team sent their vaccination to the Argonne National Laboratory and allowed them to be put to the test by vaccinating mice before infecting them with high doses of the SARS-CoV-2 virus. One hundred percent of mice treated with the SNA vaccine survived through the end of the experiment with no lung damage caused by COVID-19 pneumonia.

Stopping future viruses

COVID-19 as a case study to evaluate how well the vaccine worked was mainly practical. It also highlights the importance of the SNA as an infectious disease platform.

COVID-19, according to Teplensky, caused a shift in behavior toward infectious diseases. People didn''t recognize and appreciated the emergent potential that infectious disease can have, Teplensky said. We saw an opportunity to use COVID as a case study to investigate the shortcomings in the vaccination area.

Distler said with this case study that although the results are excellent, the objective was not to compete with existing COVID vaccinations. Were you 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 might even be used to target something as complex as HIV.

This approach is modular, meaning that a quick turnaround may only be required to develop a new vaccine for a future virus, mainly if what we previously observed with the cancer vaccination works, according to Mirkin. All we need to do is alter what was teaching the immune system to target.

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