[R01] Multi-target mucosal immunotherapies via engineered biomaterials
Ente: National Institute of Allergy and Infectious Diseases
Scadenza: 2031-06-30
Importo max: 684.405 EUR
Paese: US
Descrizione
Although it is well recognized that diseases of mucosal tissues are driven by deeply intertwined dysregulation
of both microbial and inflammatory processes, modern treatment of these diseases primarily tackles each
component separately, with few exceptions. This existing practice misses opportunities to systematically
investigate and optimize integrated and tailored therapies so that they can address both microbial and
inflammatory components synergistically. It also means that multiple medications must be either formulated
together or co-prescribed and managed by physicians, favoring one-size-fits-all products poorly matched to
specific diseases and burdening the US healthcare system by requiring active management of complex drug
mixtures. This situation has arisen because there have yet to be platforms developed that target microbes and
inflammatory mediators in an integrated and modular fashion so they can be systematically investigated and
optimized in the context of specific diseases. Our research group has made significant advances recently in
pioneering modular supramolecular (self-assembling) polypeptide nanomaterials that can raise highly
controllable neutralizing antibody responses against microbial and inflammatory targets. We term this approach
Immunomodulation via Self-Assembled Peptides (ISAP), and we have recently designed mucosally active
ISAP variants individually targeting bacterial virulence factors as well as inflammatory mediators such as
cytokines, inflammatory complement components, and natural antibody targets such as phosphorylcholine.
This prior work now enables the current project, which focuses on designing mucosal ISAP towards two
diseases with complex inflammatory/microbial etiologies: recurrent urinary tract infections (rUTI) and
inflammatory bowel disease (IBD), namely colitis. The project will be undertaken by an interdisciplinary group
bridging biomaterial engineers (Joel Collier Lab) with experts in the clinical treatment and basic investigation
of rUTI (Nazema Siddiqui Lab) and IBD (Laura Hale Lab). The aims are 1) to establish design rules for
controlling the kinetics and durability of antibody and cellular responses raised by ISAP, 2) to optimize ISAP to
raise combined neutralizing responses against selected microbial and inflammatory targets in the genitourinary
and gastrointestinal tract, and 3) to maximize therapeutic efficacy in two preclinical models of mixed
microbial/inflammatory etiology: rUTI and colitis. Collectively, this project will design immunotherapies expected
to have enhanced efficacy for treating rUTI and colitis, and it will establish a novel approach for tackling both
the microbial and inflammatory aspects of multiple mucosal diseases in an integrated fashion.
Istituzione: DUKE UNIVERSITY
PI: Joel H Collier
Progetto: 1R01AI201850-01
Settori: National Institute of Allergy and Infectious Diseases
Vai al bando originale
Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.