Studying how microbiome affects immunity could improve vaccine effectiveness

AMES, Iowa – So many microbes live in and on your body that it might be helpful to think of them functioning collectively as a separate organ. That’s because these tiny organisms that live primarily in our gut, collectively known as the microbiome, often perform helpful functions that keep the body running smoothly.

Scientists at Iowa State University are employing innovative artificial intelligence to study how the microbiome interacts with the human immune system. The research group recently received a grant from the U.S. Department of Defense to study how the microbiome could be modified to make vaccines more effective. The first year of the grant totals around $550,000, with options for two additional years for an estimated total award of $1.6 million.

Dr. Gregory Phillips, a professor of veterinary microbiology and preventive medicine at the ISU College of Veterinary Medicine and principal investigator on the grant, said the researchers are focusing on gut bacteria that have adapted to live in the human digestive system. These bacteria interact with the host systems to promote health in various ways.

“They’ve got an environment in our guts where they can thrive and grow and utilize what we feed them, and they help our digestive system by converting some of the food we eat that we don’t have the capacity to break down,” Phillips said.

Microbiome & immune response

A healthy microbiome also affects the immune system, and the research team will look for parts of the microbiome that influence the effectiveness of vaccines. As the coronavirus pandemic has shown, not everyone responds to vaccines in identical ways. The level of immunity conferred by a vaccine, as well as the durability of that immunity, can fluctuate from one individual to another. Phillips and his colleagues will study whether conditions in the microbiome can improve vaccine response. For instance, are there particular bacteria whose presence strengthens vaccine response, or even particular genes within bacteria? And can humans adjust their microbiomes to optimize their vaccine response, such as through the use of probiotics?

Phillips will lead trials in mice monitoring changes in microbiota spurred by vaccine delivery and immune response. But because the interactions the researchers are watching are so complex, the experiments will generate vast amounts of data. That’s why Phillips has teamed up with scientists at Indiana University to apply machine learning to find patterns in all that data.

They hope to find definitive, cause-and-effect relationships between the microbiome and immune response. The sheer complexity of those interactions will present a major challenge, he said.

“As scientists, we want to find cause and effect,” he said. “We want to go beyond associations to get at causes, something in the microbiota that influences the host whereby vaccines can be improved.”

Phillips said the collaborative nature of the ISU Nanovaccine Institute, a consortium of 75 researchers at 23 institutions, laid the foundation for the project to move forward. The institute fosters partnerships among researchers from different disciplines, which was a key in bridging the gap between biology and artificial intelligence.

“The Nanovaccine Institute has many disciplines that you wouldn’t ordinarily put together under one roof,” Phillips said. “Iowa State is doing a good job in seeing the importance of these multidisciplinary interactions.”

Military applications and beyond

The Department of Defense is funding the research because of its interest in keeping warfighters at peak physical health. Phillips said the U.S. sends military personnel across the globe, where they might encounter a wide range of viruses and pathogens. Improving vaccine response is an important way of ensuring these personnel stay healthy and active in their missions.

But the research also could have implications beyond military applications, Phillips said. The researchers will test vaccines that target the spike protein of the SARS-CoV-2 virus to gauge whether changes in the microbiome can improve immune responses to COVID-19. It’s likely their findings will apply to the health of pets and production animals as well.

Phillips will serve as the principal investigator for the overall project and will oversee the animal microbiome experiments at Iowa State. Dr. Michael Wannemuehler, a professor of veterinary microbiology and preventive medicine and a Nanovaccine Institute researcher, also will contribute. Dr. Paul Macklin at Indiana University will serve as a co-principal investigator and lead the AI-modeling. Dr. Aarthi Narayanan, director of translational research and technology transfer at the Virginia-based nonprofit American Type Culture Collection, will lead the viral challenge experiments.