Adjuvants supercharge existing COVID-19 vaccines in mice

Researchers have found a way to supercharge existing COVID-19 vaccines so they generate a more potent immune response at a lower dose than the ones currently in use, at least in mice.

Researchers at Massachusetts Institute of Technology (MIT) said the findings could eventually form the basis of intranasal vaccines against COVID as well as improve RNA vaccines more broadly, according to a Sept. 7 article in Nature Biomedical Engineering.

“The mRNA vaccine platform has revolutionized the way we think of vaccine development for ease of production and delivery,” Nirbhay Kumar, Ph.D., a professor of global health at George Washington University who was not affiliated with the study, told Fierce Biotech Research in an email. “There is always room for further improvement and in that sense the studies are exciting.”

Boosting vaccine potency by adding what’s known as an adjuvant to the formula is a common practice for non-RNA vaccines. Adjuvants work in various ways depending on the type; some induce immune cells, like cytokines and chemokines, while others enhance the presentation and uptake of the antigen.

There are non-RNA COVID-19 vaccines that contain adjuvants. Novavax’s vaccine—which works by presenting the spike protein of the SARS-CoV-2 virus to the immune system so it can form antibodies—contains Matrix-M, a compound that includes extracts from the soapbox tree that enhance immune cell activation. GSK, well known for its adjuvant technology, has an adjuvanted-protein-based vaccine called SKYCovione in clinical trials through a collaboration with SK bioscience. GSK also worked with Novavax to manufacture its vaccine.  

Until now, no one had tried adjuvanting mRNA-based COVID vaccines like the ones from Moderna and Pfizer-BioNTech. To do so, the MIT team tweaked the mRNA that encoded the COVID-19 antigen so the mRNA not only encoded the virus’s spike protein but also a protein called C3d. C3d is what’s known as a complement protein because it stimulates the complement arm of the immune system—the portion that “complements” antibodies by activating additional inflammatory processes or killing pathogens directly.

The researchers also wanted to see whether altering the lipid nanoparticle that delivers the mRNA could boost the immune response, too. Unsure of what chemical structure would best optimize the response, the researchers developed a library of 480 lipid nanoparticles and tested them out with the newly adjuvanted vaccine. From there, they “identified some chemistries that seemed to improve their response,” study lead Daniel Anderson, Ph.D. said in a press release from MIT.

The team then put their new vaccine to test in mice, pitting it against a non-adjuvanted mRNA vaccine to see which induced a greater antibody response. Intramuscular injections of the adjuvanted vaccines induced 10 times the amount of antibodies as the standard one, along with a greater response in T cells. The scientists saw similar results with intranasal administration, a design that could make COVID vaccines inherently more effective by placing a shield at the virus’s primary entry point.

“This reduction in required dosage, paired with the possibility of intranasal administration, could enable a quicker response to emerging infections," the researchers wrote in their paper.

The vaccines are still a way off from being ready for testing in humans; the findings will need to be replicated in primates first, and any formulation modifications will have to be tested for toxic side effects, Kumar noted. Still, they have significant implications for both COVID-19 vaccines as well as those for other diseases, such as the mRNA vaccine his lab is developing for malaria.

“There are new COVID variants already in circulation and a vaccine that can be developed easily and gives long lasting immunity could be a game changer,” Kumar said. “Our own [George Washington University] research on malaria vaccines can benefit from discoveries like the ones reported in this study.”

Anderson's team is now studying how well the strategy works with other types of RNA vaccines, including ones against cancer. It's also collaborating with healthcare companies to test the new vaccines out in larger animal models, according to the release from MIT.