A new class of biomaterial developed by Cornell researchers for an infectious disease nanovaccine effectively boosted immunity in mice with metabolic disorders linked to gut bacteria – a population that shows resistance to traditional flu and polio vaccines. So, the study is the first to explore the interrelationship among nanomaterials, immune responses and the microbiome, an increasingly important area of research. The microbiome – the collection of microorganisms living in the body – is believed to play a critical role 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 published in Science Advances.
The performance of established nanovaccines
“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.”More than a third of Americans and a quarter of people worldwide; believed to suffer from metabolic syndrome, an umbrella for several disorders including obesity, inflammation and insulin resistance.
The gut microbiome is among the factors that can cause metabolic syndrome, and researchers are interested in microbiome-induced metabolic syndrome because of evidence linking both the microbiome and metabolic disorders to the immune system. “Understanding how the microbiome affects future engineered vaccines is of utmost importance from a public health perspective,” said Ilana Brito. “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.”
New nanomaterial vaccines
However, previous research showed that traditional human flu and polio vaccines; fail 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. So, nanovaccines, generally composed of nanomaterials; taken up by cells in the immune system; and found to induce stronger immunity; than traditional soluble vaccines in pre-clinical models.
But researchers found that the most widely used type of nanovaccine; made of poly(lactic-co-glycolic acid) (PLGA); is not very effective in mice with gut-initiated metabolic syndrome. When researchers tested PLGA nanovaccines on the mice; it was less successful than they had expected; even with the addition of a widely 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.”
“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 in conclusion. “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.”