Mice with metabolic diseases linked to gut bacteria seem to show resistance to traditional flu and polio vaccines. In a study published yesterday in Science Advances, researchers were able to boost immunity in these mice using a nanovaccine made with a newly developed class of biomaterial.

“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,” says senior author Ankur Singh of Cornell University. “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 quarter of people worldwide are believed to suffer from metabolic syndrome—an umbrella term 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.

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“This research will open up new avenues for exploring how specific components of the microbiome alter immune responses,” says co-author Ilana Brito. “When engineering new vaccines, it’ll be important to design materials that are effective across a diversity of microbiome compositions.”

Nanovaccines, which are generally composed of nanomaterials, can be taken up by cells in the immune system and have been found to induce stronger immunity than traditional soluble vaccines in pre-clinical models. But the researchers found that the most widely used type of nanovaccine, made of PLGA, is not very effective in mice with gut-initiated metabolic syndrome.

“We asked, are there ways to overcome this restricted response by engineering new nanomaterial vaccines?” Singh says. “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 formed a stable nanogel with protein antigens, which was found to be effective under gut-initiated metabolic syndrome conditions. They discovered that this new material stimulates a receptor that recognizes 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,” says co-author Cynthia Leifer, “which likely contributes to their stronger immune activation and ability to overcome limitations imposed by diseases or altered microbiomes.”