The Pfizer and Moderna COVID-19 vaccines have proven to be incredibly effective at fighting the pandemic. Both of these vaccines are made using messenger RNA (mRNA), the genetic material that contains instructions for cells to build antigen proteins. These mRNA vaccines represent a fundamentally different approach to traditional vaccines.
Essentially, all vaccines are used to stimulate and train the body’s immune system to recognize and destroy pathogens. Traditional vaccines contain either killed or weakened forms of a virus or bacterium or proteins associated with the pathogen to provoke an immune response. Rather than introducing a pathogen or associated protein directly, mRNA vaccines introduce genetic information that instructs cells to make proteins that are associated with the pathogens, triggering an immune system response.
While mRNA vaccines have several major advantages over traditional vaccines – precise immune responses, rapid development and production processes, inherent safety – there are a few significant drawbacks. The most critical of these is the overall thermal instability of RNA, which begins to break down above freezing temperatures. As a result, mRNA vaccines require stringent cold chain conditions for manufacturing, storage and worldwide distribution (-20°C for Moderna, -80°C for Pfizer-BioNTech vaccines), which has hindered the widespread utilization of them, particularly in rural areas and developing countries that lack ultracold freezers and cold-chain assurance. To make mRNA vaccines much more broadly accessible, it is critical to improve mRNA vaccine stability while maintaining efficacy and safety.
A team lead by Dr. Qing Sun, assistant professor in the Artie McFerrin Department of Chemical Engineering, has been awarded a Texas A&M University X-Grant to examine and find solutions to the problems presented by mRNA vaccines. This team is composed of eight faculty members, including Sun, Dr. Arum Han, Dr. Xiaoning Qian and Dr. Yang Shen from the College of Engineering; Dr. Paul de Figueiredo, Dr. Julian Leibowitz and Dr. Jim Song from the Texas A&M University School of Medicine; and Dr. Xiuren Zhang from the Texas A&M University College of Agriculture and Life Sciences. The overarching goal of the project, titled “A Multidisciplinary Platform to Develop Thermally Stable and Highly Efficient mRNA Vaccines,” is to develop an integrated platform that includes high throughput deep learning and novel experimental systems that predict and produce thermally stable mRNA vaccines.
The X-Grant team will develop a machine-learning platform that utilizes deep learning to predict the thermal stabilities of various RNA from sequence information. The team will then develop a DNA/RNA synthesis platform that supports the prototyping of mRNA vaccines and tests the immunogenicity/efficacy of each of the prototype vaccines. The research will initially focus on COVID-19, but the goal is to make the platform flexible enough to expand into other infectious agents, cancers and other significant human diseases.
X-Grants, part of the President’s Excellence Fund at Texas A&M University, is an interdisciplinary program designed to bring faculty together across disciplines. The program’s goal is to unlock creative and imaginative ideas that will address important problems in areas that will significantly impact the most important challenges facing global society. For round four of the X-Grants program, there were more than 200 proposals submitted to the program and eight were finally funded.