Bacterial proteins often play a successful hide and seek game with the body's immune system, making it difficult to combat the bacteria that cause diseases like staph infections.
Now, biomolecular engineer Aditya Kunjapur and colleagues have come up with a strategy to create bacteria that build and incorporate a key amino acid into their own proteins, which makes the proteins more "visible" to the immune system.
For this work toward building a better platform for possible future bacterial vaccines, Kunjapur is the winner of the 2024 BioInnovation Institute & Science Prize for Innovation. The prize seeks to reward scientists who deliver research at the intersection of the life sciences and entrepreneurship.
"Dr. Kunjapur's outstanding research demonstrates the potential to engineer live bacterial cells to produce and incorporate nitrated amino acids into antigenic proteins, thus shining a spotlight on these proteins for the human immune system," said Michael Funk, senior editor at Science. "This work provides a platform for antigen engineering that is adaptable, specific, and amenable to safety controls."
In his winning essay published April 5 in Science, Kunjapur, an assistant professor of chemical and biomolecular engineering at the University of Delaware, writes that "our primary hypothesis is that engineering cells to access a broader chemical repertoire of building blocks can improve live bacterial vaccine efficacy."
One of the building blocks that caught Kunjapur's eye came from previous research that modified a bacterial protein with a non-standard amino acid called para-nitro-L-phenylalanine (nitro-Phe). These nitrated proteins triggered sustained production of antibodies in mice, suggesting that the altered amino acid was making the bacterial protein easier to access or easier to recognize by the immune system.
Kunjapur and colleagues have now programmed E. coli bacterial cells to synthesize their own nitro-Phe and incorporate it into target proteins. These altered proteins could someday become the basis for a live bacterial vaccine, the researchers suggest.
"In principle, the nitro-Phe modified protein produced by the engineered bacteria within a patient would lead to a targeted, sustained, and protective immune response towards bacterial pathogens that contain the wildtype form of the protein," Kunjapur writes.
Kunjapur's research team used E. coli as a proof-of-concept for their bioengineering strategy, but he said the strategy could work with other bacteria as well, including those that might be better at targeting certain pathogens or even tumor tissue.
"We could also continue to use E. coli as a platform vector that makes recombinant proteins that belong to other bacteria," he said. "So you can pick your chassis or your protein delivery vehicle, but the proteins you choose to nitrate should determine what immune cells respond to."
"While we have a platform technology with several promising directions, one attractive indication would be a vaccine for staph infections," Kunjapur added. The need for a staph vaccine was emphasized in meetings Kunjapur's postdoc Neil Butler held with individuals from pharmaceutical companies, clinical trial operators, and hospital staff as part of his participation with the U.S. National Science Foundation Innovation Corps program.
Vaccines against bacterial infections would likely decrease the need for antibiotic medicines, which in turn could stem the development of antibiotic resistance in some key drugs. Kunjapur said bacterial vaccines have an estimated global market size of $39.6 billion by 2030.
Finding funding for filing intellectual property was a challenge during the years of the pandemic, and Kunjapur used his own funds for his Patent Cooperation Treaty patent application. "At the time I had cautious optimism in investing in new potential vaccine modalities during the height of a pandemic, but a lot of it was also a bet on the people behind the idea and our collaborators," he said.
Kunjapur co-founded Nitro Biosciences, Inc. with Butler to pursue the nitro-Phe technology. He said starting the company has made him think more about who is going to use the technology, and what kind of criteria and metrics they need to know so that it can be used successfully.
"It's a shame that a lot of academic work has the potential to make a difference in people's lives, but academics aren't ordinarily incentivized or trained to think about what the customer needs, who the customer is, and how do you advance the technology to the stage where it could be in the clinic," Kunjapur said.
In his lab at the University of Delaware, Kunjapur and his students are also working on other bioengineering projects with environmental applications, including containment strategies "to prevent a genetically modified organism like bacteria from surviving where and when it shouldn't."
"This year's finalists have conducted some truly exceptional research and the standard of all entries was extremely high," said Jens Nielsen, chief executive officer at BioInnovation Institute. "Their work combines cutting edge science with entrepreneurial spirit, aligning with BII's goals of improving human and planetary health."
FINALISTS
William Wasswa is a 2024 finalist for his essay, "Automated innovation and impact. Wasswa received a bachelor's degree from Mbarara University of Science and Technology (MUST), a master's degree from the University of Cape Town, and a Ph.D. from MUST, where he spent some time at the University of Strathclyde, UK under the Commonwealth Ph.D. split-site scholarships. He completed his postdoctoral fellowship under the AfyaBora Global Health Leadership Fellowship program and an Innovations & Entrepreneurship Fellowship from the Royal Academy of Engineering. In 2020, he started his Medical Imaging and Artificial Intelligence Laboratory in the Department of Biomedical Sciences and Engineering at MUST and a Digital Health Unit at Global Auto Systems LTD. His research and innovation work is focused on the development of low-cost digital technologies to support the diagnosis, treatment and management of cancer in Africa.
Khalil Ramadi is a finalist for his essay, "Edible electronics to treat the brain." Ramadi received an undergraduate degree from Pennsylvania State University and a PhD from the Massachusetts Institute of Technology. After completing his postdoctoral fellowship at Brigham and Women's Hospital, Ramadi started his laboratory in the bioengineering department at New York University Abu Dhabi in 2020. His research focuses on developing neurotechnologies for improved therapy of neurologic, metabolic, and immune disorders.
