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). 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 in an effort 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,” says Steven M. Dubinett, MD, 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.”
Adds Tracy Johnson, PhD, dean of the UCLA College of Life Sciences: “By bringing 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.”
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, says Elaine Hsiao, PhD, 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,” says Dr. 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.”
Dr. Hsiao notes 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 says. “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.
“It has been recognized for many years that microbes can promote cancer, with H. pylori as a classic example,” says Jonathan Jacobs, MD, PhD, associate professor in the UCLA Vatche & Tamar Manoukian Division of Digestive Diseases, GLMC co-director, and leader of one of the funded MVP projects. “But with recent advances in microbiome research, many more are being identified, such as Fusobacterium nucleatum. It’s become apparent that to effectively prevent or treat cancer that’s driven by these microbes, we need new tools to target them.”
Dr. Jacobs notes 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,” Dr. Jacobs says. “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.”
MVP’s eight funded research projects are tackling cancer-linked pathobionts through a variety of strategies — taking “multiple shots on goal,” as the program’s leadership refers to it.
The approaches fall into three pillars:
Developing precision antimicrobials: Projects in this pillar are seeking to identify and deploy antimicrobials that more precisely target the pathobiont, as opposed to the broad-spectrum antibiotics currently used.
Boosting the immune system: Projects in the second pillar aim to find ways to use the microbiome to amp up the immune system’s ability to fight the pathobiont through non-traditional approaches.
Strengthening microbial communities: Research under the third pillar is based on the concept that the cancer-promoting bacteria require a strong foothold in the GI tract. These projects aim to boost the immune response by building microbial communities that strengthen the barrier of defense against pathobionts — a strategy that builds on the successful approach used in fecal transplants for C. difficile infection.
Drs. Hsiao and Jacobs point out that the failure to develop effective vaccines against H. pylori has highlighted the limitations of traditional single-discipline approaches. GLMC, which is overseeing the early-stage basic research for MVP, is well suited to overcome those shortcomings. The center embodies the breadth of scientific expertise at UCLA and the culture of interdisciplinary collaboration on the campus, with investigators from 11 laboratories spanning microbiology, immunology, vaccinology, structural biology, computational biology, gastroenterology and translational science.
“Overcoming past challenges will require expertise drawn from across these distinct fields,” Dr. Jacobs says. “The synergies gained by close coordination among the 11 investigative teams — including sharing data, reagents, biospecimens and technical expertise — will accelerate the discovery process.”
That interdisciplinary foundation is further strengthened through the partnership with CIII. CIII brings together leading experts in immunology within a collaborative, industry-inspired model designed to accelerate the translation and commercialization of the most promising scientific discoveries so that they can more rapidly reach patients.
“This work is emblematic of why we established the CIII and microbiome institute in partnership with UCLA,” says Gary K. Michelson, MD, a philanthropist who is founder and co-chair at Michelson Philanthropies, and chair of the CIII. “It is difficult if not impossible to replicate the scientific expertise that the campus brings to immunological discovery.”
“We’re excited to partner with the California Institute of Immunology and Immunotherapy,” Dr. Hsiao says. “At GLMC, our expertise lies in basic-science discovery that can inform the development of new therapeutics. Through this pipeline partnership, GLMC can conduct early-stage research and discovery, while CIII-affiliated groups can advance the most promising discoveries toward human translation and commercialization.”
Dr. Hsiao believes the partnership’s unconventional structure positions the MVP to bring effective microbiome-based treatments closer to the clinic.
“MVP is being run like an industry program,” she says. “Unlike traditional exploratory academic research, it’s milestone-driven and team-based. There is shared urgency to develop better treatments while maintaining the highest standards of rigor. By the end of our current funding cycle, we aim to have promising candidates that can move forward into human studies.”
