A chitosan-based nanosystem as pneumococcal vaccine delivery platform. 2021

Sandra Robla, and Maruthi Prasanna, and Rubén Varela-Calviño, and Cyrille Grandjean, and Noemi Csaba
Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, A Coruña, Spain.

Chitosan-based nanosystems have been described as interesting tools for antigen delivery and for enhancing the immunogenicity of nasally administered vaccines. As a possible vaccine delivery method, the chemical conjugation of chitosan nanocapsules with the Streptococcus pneumoniae cell membrane protein PsaA (pneumococcal surface adhesin A) is suggested here. The antigen PsaA, common to all pneumococcus serotypes, is expected to improve its uptake by immune cells and to activate specific T cells, generating an adaptive immune response against pneumococcus. With this aim, chitosan nanocapsules with thiol-maleimide conjugation between the polymer (chitosan) and the antigen (PsaA) were designed to enable the surface presentation of PsaA for immune cell recognition. Spherical-shaped particles, with a size of 266 ± 32 nm, positive charge of +30 ± 1 mV, and good stability profiles in simulated nasal fluids (up to 24 h) were achieved. PsaA association rates were three times higher compared with nanocapsules without covalent polymer-protein conjugation. Cytotoxicity studies in cell culture media showed non-toxic effect under 150 µg/mL concentration of nanocapsules, and subsequent studies on the maturation of immature dendritic cells in the presence of antigen-conjugated nanocapsules displayed peripheral blood mononuclear cell activation and lymphocyte differentiation after their presentation by dendritic cells. Secretion of TNFα following exposure to nanocapsules and the ability of nanocapsules to activate CD4 and CD8 T lymphocytes had also been studied. Antigen loaded nanocarrier uptake and presentation by professional presenting cells.

UI MeSH Term Description Entries
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D013296 Streptococcus pneumoniae A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals. Diplococcus pneumoniae,Pneumococcus
D048271 Chitosan Deacetylated CHITIN, a linear polysaccharide of deacetylated beta-1,4-D-glucosamine. It is used in HYDROGEL and to treat WOUNDS. Poliglusam
D018829 Adhesins, Bacterial Cell-surface components or appendages of bacteria that facilitate adhesion (BACTERIAL ADHESION) to other cells or to inanimate surfaces. Most fimbriae (FIMBRIAE, BACTERIAL) of gram-negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. What is sometimes called polymeric adhesin (BIOFILMS) is distinct from protein adhesin. Adhesins, Fimbrial,Bacterial Adhesins,Fimbrial Adhesins,Adhesin, Bacterial,Bacterial Adhesin
D022242 Pneumococcal Vaccines Vaccines or candidate vaccines used to prevent infections with STREPTOCOCCUS PNEUMONIAE. Pneumococcal Polysaccharide Vaccine,Pneumococcal Vaccine,Pneumovax,Pnu-Imune Vaccine,Pnu Imune Vaccine,PnuImune Vaccine,Polysaccharide Vaccine, Pneumococcal,Vaccine, Pneumococcal,Vaccine, Pneumococcal Polysaccharide,Vaccines, Pneumococcal

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