Hybrid mRNA and protein vaccine induce 5x more antibodies in mice
Caltech scientists have developed a new type of vaccine that works like a hybrid of mRNA and protein nanoparticles. In tests in mice, the prototype produced five times more antibodies than existing COVID-19 vaccines, and could be put to work against a range of diseases.
The general principle of a vaccine is to train a person’s immune system to recognize a pathogen, such as influenza or SARS-CoV-2 viruses, so that they can more effectively fight them off during future infections. This is usually done by introducing proteins from the target to the body, so the immune cells create effective antibodies against them.
Protein-based vaccines, such as Novavax’s COVID-19 vaccine, directly deliver inactivated versions of a pathogen's proteins that circulate and attract the attention of the immune cells. But mRNA vaccines, which have been in development for decades before being accelerated by the COVID-19 pandemic, take a different approach. These use mRNA molecules that teach the body’s own cells to produce pieces of virus proteins, which in turn trigger an immune response.
The Caltech team has now developed a new technique that combines both methods into one vaccine. Known as ESCRT-and ALIX-binding region (EABR) technology, the vaccine uses mRNA to coax the recipient’s cells to make protein fragments, but also includes little “tails” on these proteins. These tails trigger cellular processes that lets some proteins clump together into virus-like particles and circulate through the body. In this way, they then function like protein-based vaccines.
“During a natural infection, the immune system encounters both infected cells and free virus particles,” said Magnus Hoffmann, lead author of the study. “Current mRNA vaccines mimic infected cells, while protein nanoparticle-based vaccines mimic free virus particles to stimulate immune responses. Our hybrid technology does both.”
The team tested the new technique as a COVID-19 vaccine in mice, and found that mice given the hybrid vaccine produced five times more antibodies than existing vaccines. Only two shots rather than three were needed to induce robust antibody levels against Omicron variants, and these antibodies were also effective against the original strain and the Delta variant.
While there’s plenty more work to do, the team says this hybrid vaccine technology could be put to use against other pathogens, like the flu and even HIV. Further afield, using the tails to build self-assembling nanoparticles could eventually be used to deliver drugs to targets like cancer cells.
The research was published in the journal Cell.