Nanovaccine enhances immunity in mice with intestinal microbiome-mediated metabolic syndrome

A new clbad of biomaterials developed by Cornell researchers for a nanovaccine against infectious diseases has effectively enhanced immunity in mice with metabolic disorders related to intestinal bacteria – a population that is resistant to traditional vaccines against influenza and polio.

This study is the first to explore the relationships between nanomaterials, immune responses and the microbiome, an increasingly important area of ​​research. The microbiome – the collection of microorganisms living in the body – is supposed to play a crucial role for human health.

"This paper highlights the impact of the microbiome on our vaccines and how to solve these problems by developing advanced materials," said Ankur Singh, badistant professor at the Sibley School of Mechanical and Aerospace Engineering (MAE ) and the biomedical engineering school of Meinig. (BME).

Singh is the lead author of "Immunomodulatory Nanogels Overcoming Limited Immunity in a Mouse Model of Metabolic Syndrome Carried by the Intestinal Microbiome", published March 27 Progress of science. The first author of the article is Matthew Mosquera, PhD student in engineering.

"These works open a new and exciting area of ​​investigation into the impact of biological factors and underlying diseases on the performance of existing nanovaccines," said Singh, also a member of the Englander Institute. for the precision medicine of Weill Cornell Medicine. Cornell Center for Immunology newly formed. "More importantly, it shows how you can use these engineering materials and make them more usable for a wider population in order to defeat immunity to vaccines."

More than a third of Americans and a quarter of the world's population would suffer from metabolic syndrome, an umbrella for several disorders, including obesity, inflammation, and insulin resistance.

The intestinal microbiome is one of the factors that can cause the metabolic syndrome and researchers are interested in the microbiome-induced metabolic syndrome because of the evidence linking the microbiome to metabolic disorders and the immune system.

"Understanding how the microbiome affects future artificial vaccines is of paramount importance from a public health perspective," said Ilana Brito, badistant professor of biomedical engineering and co-author of the paper. "This research will open new avenues to explore how specific components of the microbiome alter immune responses.When designing new vaccines, it will be important to design effective materials for all microbiome compositions."

Previous research has shown that traditional influenza and polio vaccines in humans fail in mice with metabolic disorders caused by disruption of their intestinal biomes. "This has motivated us to examine what is happening with nanovaccines, which may be better than soluble vaccines, to better understand the role of underlying obesity and inflammation that thrive in alterations of the intestine, "said Singh.

Nanovaccines, which are generally composed of nanomaterials, can be absorbed by cells of the immune system and have been shown to induce stronger immunity than traditional soluble vaccines in preclinical models.

But researchers found that the most widely used type of nanovaccine, based on poly (lactic-co-glycolic acid) (PLGA), was not very effective in mice with metabolic syndrome of intestinal origin. When researchers tested PLGA nanovaccins on mice, the results were less convincing than expected, even with the addition of a widely used immunostimulator.

"We asked if there were ways to overcome this limited response by developing new vaccines for nanomaterials." Said Singh. "Then we went into a new clbad of substances that modulate the immune system, pyridine-functional poly (2-hydroxyethyl methacrylate), whose potential we recently discovered."

The new material formed a stable nanogel with protein antigens, which proved effective in conditions of metabolic syndrome caused by the intestine. In collaboration with Cynthia Leifer, Associate Professor of Immunology at the Faculty of Veterinary Medicine, the group 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 provide both an antigen and an adjuvant without the need for additional immune booster, which probably helps to enhance their immune activation and their ability to overcome the limitations imposed. by altered diseases or microbiomes, "said Leifer. "Immunomodulatory therapies are a hot topic, and materials-based immunomodulation approaches are in their infancy, and we can do a lot."

Although it has been established that the microbiome has an impact on the immune system, these results suggest that nanovaccines may have an influence on the microbiome back.

"Nanomaterials can modulate the composition of the gut microbiome – I think it's extremely important for the whole field and it could have implications for the design of materials," he said. "Whether it's a causative effect or the reason behind it is not very well understood – there are still several hypotheses to test, so it will be a future job for us."