April 10, 2023
By Rose Miyatsu
Three years ago, Robert Coffman, adjunct professor of biomolecular engineering at UC Santa Cruz, formally retired from his position as chief scientific officer of Dynavax Technologies. After a long, successful career, he was hoping to take things easy while continuing his interdisciplinary collaborations with professors at UC Santa Cruz. Then the pandemic hit, and Dynavax’s phones began ringing off the hook. Before it had really begun, Coffman’s retirement was cut short.
Coffman is an expert immunologist who has spent decades studying ways to enhance the human innate immune response. During his time at Dynavax, he led them to develop vaccine adjuvants, the components in a vaccine used to help stimulate a more powerful immune response. Now his skills were being called on again to help create vaccines for COVID-19.
Understanding adjuvants
To understand what an adjuvant is and why Dynavax’s phones were ringing off the hook, it is helpful to understand the different types of vaccines and how they work.
When the COVID-19 pandemic began and almost every country that had the capacity to do so began trying to make a vaccine, they each had a decision to make between three main methods: mRNA, viral vector, or traditional vaccine technology.
Viral vector and mRNA vaccines are relatively new and use the body’s own machinery to create a copy of a harmless portion of the pathogen, in this case a version of the COVID-19 spike protein. They differ from one another in their method for delivering to the recipient cells the “instructions” for how to make the protein, but once the protein is made, they stimulate a similar immune response. The immune system recognizes the spike protein as “foreign” and produces antibodies and blood cells called T cells to defend against the virus. Moderna and Pfizer are both mRNA vaccines, and Johnson and Johnson and Oxford–AstraZeneca are viral vector vaccines.
A third, more traditional method of vaccine development used in many projects throughout the globe (including the Novavax vaccine approved in the U.S.) uses purified parts of the actual pathogen to create an immune response. These vaccines only use a part of the pathogen, such as the spike protein, so the immune system can learn what to protect the body against without being exposed to the whole virus. There are advantages to these types of vaccines, mainly that they do not need to be kept as cold as mRNA vaccines, but they also face a challenge in development because the partial pathogen, unlike the viral vector and the mRNA, does not always create enough of an immune response by itself to make the vaccine effective.
“That is where the Dynavax technology became very important,” Coffman said.
The technology Coffman developed at Dynavax is called an adjuvant, a component of vaccines that enhances the immune response by turning on a person’s innate immune response. This, in turn, stimulates the immune system’s T Cells and B Cells, leading to a rapid and high production of antibodies.
One of the adjuvants he helped create is the key component of Dynavax’s FDA-approved Hepatitis B vaccine, which was found to be more effective than traditional adjuvants in stimulating a strong response. However, this adjuvant needed modifications to be used in COVID-19 vaccines. Typically, this type of work could take as long as a decade, but with a global emergency at hand, the clock was ticking.
“I spent the next 18 months working from home and developing appropriate adjuvants for projects all over the world,” Coffman said. “As a pioneer of this technology, it was sort of up to me to adapt it.”
Coffman met regularly with the vaccine producers, as well as the Bill and Melinda Gates Foundation, which was able to use its broad network and knowledge of current vaccine projects to make connections with projects that could benefit from an immune enhancer.
Coffman and his team reformulated Dynavax’s adjuvant so that it was able to stabilize the COVID-19 spike protein, and advised a number of projects on how to use this adjuvant in their vaccines. Not all of these projects were completed, but four approved vaccines out of India, China, Taiwan, and the EU ended up using the Dynavax technology. Collectively, these vaccines have been used on over 100 million people throughout the world.
“I was very grateful for the opportunity to be able to do something at a time when so many people felt so helpless,” Coffman said. “It was a very gratifying and satisfying way to wrap up an active research career.”
Renewing interdisciplinary collaborations
Now that the emergency of the pandemic has subsided, Coffman is more traditionally retired from Dynavax and has renewed his adjunct position with UC Santa Cruz. He is hoping to mentor students and provide guest lectures and occasional classes in his area of expertise, as he did before the pandemic.
Coffman has known David Haussler, the scientific director of the UCSC Genomics Institute, since Coffman became an adjunct faculty member in 2010. They have worked together on projects, including a large program project grant aimed at understanding vaccine responses. Coffman said this work provided data that ultimately helped Dynavax receive FDA approval for their original Hepatitis B vaccine adjuvant. Coffman enjoys these kinds of cross-disciplinary discussions and collaborations, which allow him to explore new areas.
“It is good to be able to renew those connections,” Coffman said. “My expertise is tangential to the core interests of the biomolecular engineering department and the Genomics Institute, but these guys keep touching on areas where I know the biology, and they dig in from the genomics side, whether it is cancer, vaccines, or immunological disease. I’ve also learned from them a good deal about areas that I wouldn’t otherwise have a good understanding of, especially in terms of how to deal with large amounts of data.”