Computer illustration of a cross-section (orange strands) of a lipid nanoparticle carrying viral mRNA
Science Photo Library / Alamy
Virus-like vaccines typically trigger strong immune reactions; however, mRNA versions are significantly quicker and less expensive to manufacture. We now benefit from mRNA vaccines that encode for virus-like nanoparticles instead of individual proteins, as is the case with current COVID-19 mRNA vaccines.
Grace Hendricks and her team at the University of Washington in Seattle have demonstrated that an mRNA version of a coronavirus nanoparticle vaccine provokes immune responses in mice that are up to 28 times stronger than those elicited by standard mRNA vaccines.
According to Hendricks, some mild but unpleasant side effects of mRNA vaccines result from the body’s immediate response to the injected mRNA and the lipid particles encapsulating it. A more potent vaccine could enable lower dosages. “This means we can maintain the essential immune response while reducing the dose, thus minimizing side effects,” she explains.
The first vaccine was comprised of a weakened “live” virus and is highly effective, yet poses risks for individuals with compromised immune systems. This was followed by inactivated vaccines containing “dead” viruses, which are safer but challenging to produce.
The advancement continued with protein subunit vaccines that generally include only the exterior proteins of the virus. These are even safer than inactivated vaccines, but airborne proteins often fail to induce robust immune responses.
As a solution, vaccine developers began embedding viral proteins into tiny spheres to create spiky structures resembling viruses to the immune system, yet as safe as protein subunit vaccines. This is achieved by modifying existing proteins to self-assemble into small spheres with protruding viral proteins known as vaccine nanoparticles.
During the pandemic, Hendricks’s colleagues worked on a COVID-19 nanoparticle vaccine called Skycovion. Although it received approval in South Korea in 2022, mRNA vaccines had already made significant advances by that time, leading to limited use of Skycovion.
mRNA vaccines are significantly faster and more straightforward to produce than protein-based vaccines, as they provide a recipe for protein assembly, while the challenging task of protein synthesis is executed by the body’s cells. The viral proteins coded by these first-generation mRNA vaccines eventually protrude from the cell surface, inducing a more effective immune response compared to free-floating proteins but still falling short of the efficacy seen with nanoparticle vaccines.
Currently, Hendricks and her colleagues have merged the advantages of both methods by developing a vaccine that consists of mRNA encoding Skycovion. After the vaccine proteins are produced within cells, they organize into nanoparticles that have shown efficacy in mouse studies.
“This was merely a proof of concept for this gene transfer,” Hendricks stated. She and her team are already advancing what they term mRNA-launched nanoparticle vaccines targeting influenza, Epstein-Barr virus (which can lead to cancer), and various other viruses.
“I am excited about the potential of mRNA-launched protein nanoparticle vaccines.” said William Sheeff from The Scripps Research Institute in California, who is working on an HIV vaccine. “My colleagues and I have published impressive immunogenicity results with two mRNA-launched nanoparticles in clinical trials and several similar particles in mouse models. This new research enhances the existing body of work.” Despite this promising trajectory, the United States has announced significant cuts to funding for the development of mRNA vaccines.
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Source: www.newscientist.com
