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Spherical Nucleic Acid Vaccine Uses Structural Design to Improve Efficacy

Conn Hastings |

A team at Northwestern University created a new type of nanoparticle-based vaccine that employs structure-function relationships during the design phase to maximize efficacy. Called a spherical nucleic acid (SNA) vaccine, the technology consists of globular DNA nanoparticles that contain a DNA sequence that can stimulate the immune system (ie. an adjuvant) and an inner portion containing an antigen, which in this case was the spike protein of the SARS‑CoV‑2 virus. Packaging the antigen and adjuvant together in this specific way resulted in impressive efficacy in a rodent model of severe COVID-19, with 100% of vaccinated animals surviving the illness. The technology can also be rapidly adapted for other viruses, and has already shown promise as a cancer vaccine.

Vaccines have come a long way, even just in the last two years, and further innovation in this space is to be welcomed in our continuing fight against COVID-19 and a host of other infectious diseases, as well as cancer. This latest technology employs a carefully designed nanoparticle, which presents adjuvant and antigen in a specific way to maximize its effectiveness.

“What makes this vaccine different than other vaccines is the approach we take to design them,” said Michelle Teplensky, a researcher involved in the study. “Even as recently 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 those components were arranged structurally and presented to the body.”

Classically, vaccine designers made sure to focus on delivering the correct antigen to allow the immune system to develop a ‘memory’ of that antigen, with a view to attacking a target pathogen later. Part of this process involves co-administering an adjuvant, which is a substance that stimulates the immune system to ensure that the correct immune reactions take place.

However, merely co-administering these important vaccine constituents as free-floating components within a syringe is somewhat haphazard, and does not guarantee that the correct cells will be exposed to the correct substances at the correct time to ensure a maximal response. These new SNA nanoparticles ensure that both components are presented to immune cells in precisely the way the vaccine designers intended.

So far, the researchers have shown that the formulation has significant potential as a COVID-19 vaccine, having previously investigated its use as a cancer vaccine. Excitingly, the Northwestern researchers also believe that it can be rapidly adapted to act as a vaccine for other infectious diseases.

“This is a remarkable demonstration of rational vaccinology — the idea that the structure of a vaccine, as opposed to just components, can have a profound influence on efficacy,” said Chad Mirkin, another researcher involved in the study. “While we have previously shown this to be the case for cancer immunotherapies, this is the first demonstration for an infectious disease.”

Study in Proceedings of the National Academy of Sciences: Spherical nucleic acids as an infectious disease vaccine platform

Via: Northwestern University

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