Cornell scientists have developed a new family of biomaterial for an infectious disease. Nanovaccine successfully boosted immunity in mice with metabolic disorders associated with gut bacteria—a population that exhibits resistance to traditional polio and flu vaccines.
The research is the first to investigate the interrelationship among nanomaterials, immune responses and the microbiome, a progressively critical area of research. The microbiome—the assortment of microorganisms living in the body—is said have a critical role to play in human health.
“This paper highlights how the microbiome can impact our engineered vaccines and how we can overcome these problems by developing advanced materials,” said Ankur Singh, assistant professor in the Sibley School of Mechanical and Aerospace Engineering (MAE) and the Meinig School of Biomedical Engineering (BME).
Singh is senior author of “Immunomodulatory Nanogels Overcome Restricted Immunity in a Murine Model of Gut Microbiome-Mediated Metabolic Syndrome,” which was published in the March 27th issue of Science Advances. The paper’s first author is Matthew Mosquera, a doctoral student in engineering.
“This work opens up a new, very exciting area of investigation into how biological factors and underlying disease conditions impact the performance of established nanovaccines,” said Singh, who is also a member of the Englander Institute for Precision Medicine at Weill Cornell Medicine and the newly formed Cornell Center for Immunology. “More importantly, it shows how you can use these engineered materials and make them more workable across a wider population to overcome immunity to vaccines.”
Over a third of Americans and a quarter of people around the world are said to suffer from metabolic syndrome, an umbrella for more than a few disorders including inflammation, obesity, and insulin resistance.
The gut microbiome is one of the factors that can cause metabolic syndrome, and scientists are interested in microbiome-induced metabolic syndrome as evidence connecting both the microbiome and metabolic illnesses to the immune system.
Understanding how the microbiome affects future engineered vaccines is of utmost importance from a public health perspective. This research will open up new avenues for exploring how specific components of the microbiome alter immune responses. When engineering new vaccines, it’ll be important to design materials that are effective across a diversity of microbiome compositions.
Ilana Brito, Study Co-Author and Assistant Professor of Biomedical Engineering, Cornell University.
Earlier research revealed that traditional human flu and polio vaccines do not work in mice that have metabolic disorders caused by disruptions to their gut biomes. “That motivated us to look into what happens with nanovaccines, which can be better than soluble vaccines, to better understand the role of underlying obesity and inflammation that develops in gut alterations,” Singh said.
Nanovaccines, which are usually made up of nanomaterials, can be absorbed by cells in the immune system and have been found to trigger stronger immunity compared to traditional soluble vaccines in pre-clinical models.
But scientists found that the most extensively used type of nanovaccine, composed of poly(lactic-co-glycolic acid) (PLGA), is not very successful in mice with gut-initiated metabolic syndrome. When scientists tested PLGA nanovaccines on the mice, it was less effective than they had expected, even with the incorporation of an extensively used immune booster.
“We asked, are there ways to overcome this restricted response by engineering new nanomaterial vaccines?” Singh said. “Then we looked deeper into a new class of material that modulates the immune system, pyridine functionalized poly(2-hydroxyethyl methacrylate), the potential of which we recently discovered.”
The new material developed a stable nanogel with protein antigens, which was found to be working under gut-initiated metabolic syndrome circumstances. Collaborating with Cynthia Leifer, associate professor of immunology in the College of Veterinary Medicine, the group learned that this new material excites a receptor that detects pathogenic danger signs on microbes.
“This study is important because it shows that these nanogels can supply both antigen and adjuvant without the need for an extra immune booster, which likely contributes to their stronger immune activation and ability to overcome limitations imposed by diseases or altered microbiomes,” Leifer said. “Immunomodulatory therapies are a hot topic, and materials-based immunomodulation approaches are in their infancy. There is so much that can be done with them.”
While it has been proved that the microbiome influences the immune system, these findings propose that nanovaccines can impact the microbiome in return.
“Nanomaterials can modulate the composition of the gut microbiome—I think that’s of tremendous importance to the entire field and could have implications in material design,” he said. “Whether it’s a causative effect or the reason behind this is not very well understood—there are several hypotheses that remain to be tested, so this will be future work for us.”
The study’s other contributors were: Christopher Hernandez, associate professor in MAE and BME; doctoral students Sungwoong Kim, Kristine Lai, Hao Zhou, and Marysol Luna; Tina Jing ‘18; Jason Guss, Ph.D. ‘18; and Pooja Reddy ‘20.
The research received support through grants from the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the National Institute of Biomedical Imaging and Bioengineering, and the National Science Foundation.