Kuklina T. Immunological properties of diphtherial toxoid immobilized on micro- and nanoparticles upon peroral immunization

The immunity of the mucosa protects epithelium from invasion and colonization with pathogenic microorganisms. Mucosa cells also take part in the engulfment and processing of food- air- derived antigens and also antigens from gut microbiota. Due to the permanent and massive antigenic loads with diverse antigens, mucosal immunity is always in active state. Investigation of the different aspects of the immune response development in mucosa will open new strategies for its defense in the future. For that reason, one of the targets of scientific community is to develop and optimize oral vaccination strategies against different pathogens. In this research we investigated and compared immunogenic and immunoadjuvant properties of the particles of different nature that bear immobilized diphtheria toxoid upon peroral immunization. We have also investigated possible approaches for the functionalization of particles-toxoid complexes for the increase induction of adaptive immunity. We choose diphtheria toxoid because of is active secretion in the site of invasion and colonization of bacteria, and induction of potent immune response in this case can be used for effective elimination of the infection. We investigated a number of different particles of different nature and size that has been conjugated with diphtheria toxoid and determined that those based on poly(D,L-lactic-co-glycoic)acid were the most effective in respect for the interaction with antigen-presenting cells, cytotoxicity and immunogenicity. We have also shown that functionalization of PLGA-based particles with chitosan increased the induction of adaptive immunity against diphtheria toxoid. Overall, we have shown the efficiency of the suggested approach for peroral immunization with diphtheria toxoid. This approach can also be taken as the reference point for the creation of similar strategies for the induction of adaptive immunity in mucosa against other antigens.