Nanoparticle Image
A more targeted vaccine that, in animal studies, shows stronger, broader, and more durable protection in a single, low dose. (Credit: Wistar Institute)

The first generation of COVID-19 vaccines have been highly effective, but also have limitations: their efficacy can wane without a booster shot, and they may be less effective against some variants. Now scientists have developed a more targeted vaccine that, in animal studies, shows stronger, broader, and more durable protection in a single, low dose.

The vaccine combines three technologies — immune focusing, self-assembling nanoparticles, and DNA delivery — into a single platform for the first time. In addition to its other advantages, the vaccine could be stored at room temperature, making it potentially easier to transport to remote or developing locations than existing mRNA vaccines, which require specialized cold storage.

The new vaccine includes a rationally engineered receptor binding domain using computational and structure-based design methodologies. The engineered receptor binding domain blocks immune distracting sites and can therefore elicit stronger levels of protective, neutralizing antibodies.

Researchers then used naturally self-assembling proteins to form nanoparticles which display these highly engineered immunogens. By arranging themselves into structures that resemble an actual virus, the nanoparticles are more easily recognized by the immune system and transported to the germinal centers, where they activate B cells which produce protective antibodies.

Using nucleic acid vaccine delivery technology similar to mRNA, the nanoparticle vaccine is encoded in DNA and delivered into cells thereby giving genetic instructions for the body to build the immunogen internally. One advantage of the DNA platform is that it doesn’t require refrigeration and it can also be quickly reformulated to target new variants.

In animal models, researchers found that the DNA delivered immune-focused nanoparticle vaccine produced much higher levels of neutralizing antibodies than the vaccine that wasn’t immune-focused.

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