Molecular Engineers Adopt Innovative Approaches to COVID-19 Vaccine

Several labs at the University of Chicago’s Pritzker School of Molecular Engineering (Chicago, IL, USA) are taking an innovative approach to vaccine development.

In order to address the coronavirus pandemic, scientists are exploring approaches to vaccine development from multiple angles. One of their approaches has been to find molecules that boost any vaccine they are added to. COVID-19 does not mutate as fast as the flu, but the same approach is useful, as scientists are exploring many different vaccine avenues for a vaccine in parallel-and these could be added to any promising candidate. There are two parts to virtually all vaccines. One part is some version of the virus in question, usually with some essential parts lopped off to make it tamer, so that the immune system can learn to recognize it. There is also an ‘adjuvant,’ which is the wake-up call for the immune system. One of the scientists’ approaches is to adjust the adjuvant to activate immune cell called CD4+ cells. These cells are protect the lungs in flu, SARS and Zika infections; and since COVID-19 tends to attack the lungs, marshalling a strong CD4+ response could offer better protection.


Another angle is to add a third component to the vaccine, made up of molecules that control how the body responds to the vaccine. These would tweak cells’ signaling processes to help the body better respond to COVID-19 with less chance of side effects. The scientists are also interested in an approach called “trained immunity” that is in a very early stage, but has significant potential. The scientists have zeroed in a particular molecule called beta-glucan, which is a nontoxic sugar molecule. They believe that injecting beta-glucan without the rest of the vaccine could boost the overall immune response against any pathogen. Instead of a true vaccine, this would instead boost a person’s initial immune response if they were infected, buying time while the immune system makes specific antibodies to COVID19. A slow-release formulation would allow the system to mount a measured response over many days. If the approach works, it could be used for any pandemic and given as a preventative to people who are most at risk, such as healthcare workers.

“The reality of vaccine work is that a lot of them won’t turn out, so it’s better to have a deep bench,” said Aaron Esser-Kahn, an associate professor of molecular engineering whose lab has rapidly shifted to address the coronavirus pandemic.

Another approach by the scientists is to work on the delivery system of the vaccine. For example, researchers can attach molecules that serve as a kind of “mailing address” to get the vaccine to the specific areas or kinds of cells they want to activate, which can enhance the effectiveness of the vaccine. The scientists aim to target lymph nodes, the organs in the body that are one of the frontlines for the immune system. Within the node, there are specific cells that trigger different types of responses. The scientists plan to induce production of a particular kind of antibody called “broadly neutralizing antibodies” that seem to act on a variety of virus strains, and thus may be able to clear several strains of the virus.

“We’ll start by making various variants of the vaccine and testing them in mice to see which drives the best response, in terms of the breadth and potency of virus-specific antibodies,” said Melody Swartz, the William B. Ogden Professor of Molecular Engineering. The scientists are also developing a way to test small amounts of human immune cells in microdevices on the benchtop, to complement the results from mice. “We’ve just started testing in mice,” Swartz said. “If all goes well, we could be ready for advanced animal studies in the early fall.”

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