New Microbiome Vaccine Program at UCLA aims to harness gut microbes and immune system against cancer-promoting bacteria
UCLA Fielding's Dr. Jonathan Jacobs, assistant professor in the Department of Epidemiology, leading study under UCLA's new Microbiome Vaccine Program.
Amid mounting evidence of the gut microbiome’s pivotal role in immune development, vaccine responsiveness and cancer biology, UCLA has established the Microbiome Vaccine Program (MVP), a joint initiative of the UCLA Goodman-Luskin Microbiome Center (GLMC) and the California Institute for Immunology and Immunotherapy (CIII).
One of the projects supported in the program is led by Dr. Jonathan Jacobs, an assistant professor in the UCLA Fielding School of Public Health’s Department of Epidemiology and associate professor in the UCLA Vatche & Tamar Manoukian Division of Digestive Diseases. Jacobs’ project is studying Helicobacter pylori (H. pylori), a major cause of gastric adenocarcinoma and key contributor to lymphoma.
“It has been recognized for many years that microbes can promote cancer, with H. pylori as a classic example,” Jacobs said. “But with recent advances in microbiome research, many more are being identified … it’s become apparent that to effectively prevent or treat cancer that’s driven by these microbes, we need new tools to target them.”
The CIII is a private-public partnership with the state of California that operates out of UCLA Research Park and is affiliated with the David Geffen School of Medicine at UCLA.
Through targeted funding mechanisms, the interdisciplinary program aims to accelerate early-stage research that integrates microbial ecology with immunology to develop microbiome-directed interventions that prevent or treat cancer by boosting the immune system or targeting cancer-promoting bacteria.
The unique partnership, which launched earlier this year, leverages the GLMC’s expertise in basic science and the gut microbiome, along with CIII’s expertise in immunology and its emphasis on translational research designed to rapidly bring promising new treatments to patients. For its initial phase, MVP has funded interdisciplinary research projects led by 11 senior investigators while also investing in early-career scientists through the MVP Fellows program. This program jump-starts the ability of senior graduate students and postdoctoral scientists to advance high-impact research alongside experienced mentors — and, in the process, to gain invaluable experience in an environment that combines the best of academia with the innovation and commercialization more characteristic of the industry setting.
“This research initiative embodies the power of interdisciplinary collaboration at a world-class research university and academic health system,” said Dr. Steven M. Dubinett, dean of the David Geffen School of Medicine and UCLA’s associate vice chancellor for research. “The ability to advance fundamental biological discoveries into novel interventions is a strength of the UCLA community.”
Dr. Tracy Johnson, dean of the UCLA College Division of Life Sciences, said the intent is to bring diverse UCLA expertise together around a shared scientific mission.
”This initiative will accelerate new biological insights into meaningful advances for researchers, clinicians and patients, and also provide exceptional opportunities for the next generation of outstanding scientists,” Johnson said.
While the gut microbiome has long been recognized for its role in health and disease, its use as a tool for developing vaccines and other immunology-based therapies represents a more recent research direction — and one that is generating considerable excitement, said Dr. Elaine Hsiao, the Goodman-Luskin Endowed Chair in Microbiome Research and director of the GLMC, which is based in the UCLA Vatche & Tamar Manoukian Division of Digestive Diseases.
“The gut microbiome is closely linked to the immune system, with a large proportion of immune cells residing in the gut,” said Hsiao, who leads one of the MVP research projects. “These immune cells not only monitor and respond to foreign substances we encounter through food and other exposures but also interact with the trillions of microbes in the gut, many of which help shape immune development and function. This creates opportunities to use our knowledge of the gut microbiome in multiple ways, whether it’s to modulate immune responses to better defend against disease, or to leverage microbes to help defend against specific pathogens.”
Hsiao said that in recent years, the concept of vaccines has expanded beyond the classic definition.
“Traditionally, vaccines expose the immune system to a pathogen or its components so that it can recognize and respond more effectively in the future,” she said. “More recently, researchers have begun exploring microbiome-based approaches, including the use of beneficial microbes or their products to modulate immune responses. This reflects a broader understanding of how immune protection may be achieved, although the central goal remains the same: harness the immune system to protect against disease.”
MVP is focusing on GI cancers that involve pathobionts - normally harmless residents of the gut microbiome that can become pathogenic under certain conditions, leading to uncontrolled growth and cancer. Fusobacterium nucleatum, a gut-associated pathobiont, has recently been linked to colorectal cancer by promoting inflammation and suppressing anti-tumor immune responses. Helicobacter pylori (H. pylori), perhaps the best- and longest-established pathobiont, is a major cause of gastric adenocarcinoma and key contributor to MALT lymphoma.
Jacobs said that although H. pylori can be treated with antibiotics, this doesn’t always eradicate the infection, and the broad-spectrum antibiotics commonly used can disrupt the gut microbiome, potentially resulting in additional health problems. These challenges, he explains, underscore the need for more targeted approaches.
“There have been decades of research on H. pylori, but a vaccine has remained elusive,” Jacobs said. “MVP is leveraging advances in microbiome, immunology and precision antimicrobials to develop novel strategies for vaccination and therapy that could be effective not only for H. pylori, but also for other recently identified cancer-promoting microbes.”
