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Sci Adv. 2019 Mar 27;5(3):eaav9788. doi: 10.1126/sciadv.aav9788. eCollection 2019 Mar.

Immunomodulatory nanogels overcome restricted immunity in a murine model of gut microbiome-mediated metabolic syndrome.

Author information

1
Meinig School of Biomedical Engineering, College of Engineering, Cornell University, Ithaca, NY 14853, USA.
2
Sibley School of Mechanical and Aerospace Engineering, College of Engineering, Cornell University, Ithaca, NY 14853, USA.
3
Department of Materials Science and Engineering, College of Engineering, Cornell University, Ithaca, NY 14853, USA.
4
Department of Microbiology, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853, USA.
5
Biological Sciences, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853, USA.
6
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
7
Englander Institute for Precision Medicine, Weill Cornell Medical College of Cornell University, New York, NY 10021, USA.

Abstract

Biomaterials-based nanovaccines, such as those made of poly(lactic-co-glycolic acid) (PLGA), can induce stronger immunity than soluble antigens in healthy wild-type mouse models. However, whether metabolic syndrome can influence the immunological responses of nanovaccines remains poorly understood. Here, we first show that alteration in the sensing of the gut microbiome through Toll-like receptor 5 (TLR5) and the resulting metabolic syndrome in TLR5 -/- mice diminish the germinal center immune response induced by PLGA nanovaccines. The PLGA nanovaccines, unexpectedly, further changed gut microbiota. By chronically treating mice with antibiotics, we show that disrupting gut microbiome leads to poor vaccine response in an obesity-independent manner. We next demonstrate that the low immune response can be rescued by an immunomodulatory Pyr-pHEMA nanogel vaccine, which functions through TLR2 stimulation, enhanced trafficking, and induced stronger germinal center response than alum-supplemented PLGA nanovaccines. The study highlights the potential for immunomodulation under gut-mediated metabolic syndrome conditions using advanced nanomaterials.

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