New mRNA vaccine platform could expand global vaccine access

Future mRNA vaccines may be even more helpful in preventing infectious diseases, like COVID-19, thanks to a new vaccine platform and preclinical research from Penn. The new platform swaps out lipid nanoparticles (LNPs) with a different kind of nanoparticle formed with molecules called ionizable amphiphilic Janus dendrimers (IAJDs) and simplifies manufacturing, making the vaccines easier and more cost-effective to produce, transport, store, and distribute.

All of this could lead to clinical trials of the new platform and would mean more access to mRNA vaccines for more people, especially individuals in remote or low-resource regions. The research is published in Science Advances by the Penn Institute for RNA Innovation at the Perelman School of Medicine and the Department of Chemistry at the University of Pennsylvania.

“As mRNA vaccines have revolutionized medicine, our goal at the Penn Institute for RNA Innovation is to further enhance this technology,” said senior author Elena N. Atochina-Vasserman, MD, PhD, an assistant professor of Infectious Diseases at Penn and a researcher at the Penn Institute for RNA Innovation. “The desire to develop a new mRNA vaccine platform came from our goal of ensuring that mRNA vaccines are accessible to everyone who could benefit from them.”

mRNA vaccines today

The world was introduced fully to mRNA vaccines during the COVID-19 pandemic when Pfizer/BioNTech and Moderna developed highly effective mRNA-LNP vaccines that prevented severe disease and death from COVID-19. Unlike traditional vaccines that contain an inactivated virus or weakened virus, mRNA vaccines deliver instructions that tell the body to produce specific antigens, generate protective immune responses, and remember the virus in the future. This foundational concept was pioneered by Penn researchers Katalin Karikό, PhD, and Drew Weissman, MD, PhD, who both received a Nobel Prize for this discovery.

The lipid nanoparticles, or LNPs, are made up of four different fat components that encase and protect the mRNA and ensure it reaches the appropriate part of the body so it can be read and trigger a protective immune-system response against a virus.

“While LNPs have worked successfully and effectively in the mRNA vaccine platform, mRNA-LNP vaccines require ultra-cold storage at -80 degrees Celsius, requiring dry ice for transportation and making shipping to low and middle-income countries difficult,” said lead author Nathan Ona, BS, a research specialist at the Penn Institute for RNA Innovation. “Manufacturing is also a multi-step process.”

Expanding on a platform’s potential

To address these limitations, Virgil Percec, PhD, the P. Roy Vagelos Professor of Chemistry at Penn developed a one-component IAJD as a replacement for LNPs. Not only are the IAJDs more stable than traditional LNPs, but scientists can use them to efficiently encapsulate mRNA with a simple one-step mixing process. Additionally, this approach eliminates the need for polyethylene glycol (PEG), a component of LNPs which some believe may be tied to severe allergic reactions in very rare cases.

After screening more than 300 IAJDs, the team identified a lead candidate, IAJD97, based on its chemical structure and ability to deliver mRNA effectively. They then created an mRNA-IAJD97 vaccine designed to protect against norovirus, a major cause of gastroenteritis. When given to mice, the mice’s bodies produced antibodies to fight off norovirus. Notably, stored mRNA-IAJD vaccines remained intact for more than four months chilled at +4 degrees Celsius, meaning they can be stored in refrigerators without the need for deep freezers or dry ice.

The future of mRNA medicine

Researchers say that, with further preclinical evaluation to establish appropriate dosing and confirm efficacy, this new one-component nanoparticle vaccine platform could be used to make norovirus vaccines and other mRNA-based vaccines for human clinical trials.

“My colleagues and I frequently collaborate with scientists worldwide to develop vaccines against the unique diseases that affect their local populations, diseases for which pharmaceutical companies and the world’s richest countries may not invest in preventing,” said Weissman. “Our research here will hopefully make the path to vaccine production and disease prevention easier for scientists with fewer resources.”

IAJDs themselves are also worth exploring further, added Atochina-Vasserman.

“While this study focused on IAJD97, other IAJD structures can be designed to deliver mRNA to specific parts of the body,” said Atochina-Vasserman. “This opens new opportunities for the development of targeted mRNA therapeutics across a range of diseases.”