In a recent study, the California Institute of Technology’s novel technology seeks to develop more effective vaccines, starting with SARS-CoV-2, the coronavirus that causes COVID-19. In mouse studies, this prototype vaccine produced five times more potent antibodies than the COVID-19 vaccines currently available. These antibodies generated by the new vaccine were effective against the original strain of SARS-CoV-2, the delta variant, and the omicron variant. The findings of this study were recently published in the journal Cell, under the title “ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines”. This research was conducted in the laboratory of Pamela Björkman, a professor of biology and bioengineering at Caltech, and led by Magnus Hoffmann.
This new candidate vaccine is referred to as a “hybrid” vaccine, as it combines features of mRNA technology used by companies like Pfizer and Moderna, and protein nanoparticle-based vaccines like Novavax. Beyond aiding in the fight against COVID-19, this technology could one day be applied to enhance vaccines against HIV, influenza, and various other pathogens.
Björkman stated, “For any vaccine or infection, antibody levels decline over time. An ideal vaccine can elicit a robust immune response, producing high levels of antibodies, mitigating infections from multiple variants of the virus, and inducing cytotoxic T-cell responses that kill infected cells, preventing severe disease and death.”
Vaccines instruct the immune system on how to recognize and combat specific pathogens, and there are various ways to achieve this. Current SARS-CoV-2 vaccines deliver genetic material (mRNA) encoding the spike protein of the coronavirus or fragments of the protein itself to teach the immune system to recognize it. This new candidate vaccine is a hybrid technology, combining both mRNA and protein-based strategies. In mouse studies, strong antibody levels against the Omicron variant were achieved after only two immunizations with the hybrid vaccine, compared to the three doses required by traditional COVID-19 vaccines.
Hoffmann explained, “During natural infection, the immune system encounters both infected cells and free virus particles. Current mRNA vaccines mimic infected cells, while protein nanoparticle-based vaccines simulate free virus particles to stimulate immune responses. Our hybrid approach encompasses both aspects.”
Barbara Wold, a professor of molecular biology and director of the Richard M. Lucas Center for Faculty Insights and Outreach at Caltech, stated, “The Lucas Center is focused on providing seeds for and accelerating the translation of research from Caltech labs. As our first Lucas Center fellow, Magnus is now leading a lab that advances EABR technology. It’s an innovative approach, building on existing cellular mechanisms to enhance and more precisely tune immune responses. From this foundation, Magnus and his new team can look forward to optimizing and expanding this hybrid approach. There’s a lot of work yet to be done, but if all goes well, they will ultimately fulfill the promise of developing more effective and enduring vaccines for a range of human diseases. That’s a home run.”