Development of mucosal vaccines based in crosslinked-mucin glycoproteins and chitosan-based nanodevices

Descripción del proyecto

Un gel mucoso biomimético para el desarrollo de vacunas por vía mucosa y la restauración de la mucosa

Los peces de piscifactoría son una fuente importante de proteínas alimentarias y nutrientes. Todas las superficies de los peces están cubiertas por una capa de moco, lo que las convierte en un modelo elegido para la investigación de las mucosas. Las mucinas (MUC) son las glicoproteínas de las superficies mucosas y proporcionan lubricación y protección contra patógenos. El quitosano es un aminopolisacárido estudiado para el tratamiento de las patologías de las MUC. El proyecto cubiform, financiado con fondos europeos, pretende evaluar un gel mucoso biomimético para la vacunación por vía mucosa y la restauración de la mucosa de peces de piscifactoría, y diseñar nanodispositivos basados en el quitosano para su carga en aplicaciones de gel mucoso biomimético. El objetivo es caracterizar los efectos del gel mucoso biomimético en las actividades fagocíticas y metabólicas y la viabilidad de las células inmunocompetentes para la optimización de un tratamiento mucoso efectivo.

Objetivo

This Project aims to evaluate a biomimetic mucus gel (BMG) for its use as mucosal vaccine and mucosal restoration for farmed fish. In addition, through a joint experimental and computational approach, rationalizing the design of chitosan (CS)-based nanodevices (ND) to load in BMG to apply on both healthy and disrupted mucosal surfaces. The aim of this project is to develop a treatment for improving animal health and welfare that are important goals in blue economy . The research work will be developed by the applicant, Dr. Collado González, in the group of Prof. María Ángeles Esteban (supervisor) at the University of Murcia (UM, host).
Farmed fish constitutes an essential way for providing dietary proteins and nutrients and they are used as a medical research model. In 2016 in EU, aquaculture resulted in about 75000 jobs and 1.3 million tonnes of aquatic animals which resulted in a gross value added of €2 billion in 2017. In fish, all surfaces are covered with mucus layer that is connected to the mucosal immunity. Mucins (MUC) are glycoproteins present at any mucosal surface . Among other functions, MUC increase lubricity of the mucosa and avoid infection by pathogens. CS refers to a family of aminopolysaccharides that have been proposed for the treatment of pathologies related to MUC. The characterization of the effects of the BMG on the metabolic and phagocytic activities as well as the viability of immune system cells will allow to optimize the BMGs to develop an effective mucosal treatment. A key issue in the development of applications in the field is that MUC and CS are families of flexible polymers with high variability in their properties and behaviour, reason why their interactions at the molecular level are difficult to unravel and not fully understood. Elucidating the main physicochemical forces behind such interactions will allow the optimization of transmucosal CS-based ND.