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A chitosan-based nanosystem as pneumococcal vaccine delivery platform

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Abstract

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.

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Antigen loaded nanocarrier uptake and presentation by professional presenting cells.

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Funding

This work was supported by ‘Ministerio de Economía y Competitividad’ (RETOS-SAF2016-79230-R-ERC2018-092841 and PID2019-108727RB-I00). Sandra Robla received financial support from the Xunta de Galicia (Centro Singular de Investigación de Galicia accreditation 2019–2022) and the European Union (European Regional Development Fund-ERDF), code ED431G 2019/02. Maruthi Prasanna received his doctoral fellowship from the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), under the Erasmus Mundus program, “NanoFar: European Doctorate in Nanomedicine and Pharmaceutical Innovation” (Project: 2015-01-C4). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Authors and Affiliations

  1. Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela, A Coruña, Spain

    Sandra Robla, Maruthi Prasanna & Noemi Csaba

  2. Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, A Coruña, Spain

    Sandra Robla & Noemi Csaba

  3. Unit Function & Protein Engineering UMR CNRS 6286, University of Nantes, Nantes Cedex, France

    Maruthi Prasanna & Cyrille Grandjean

  4. Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, A Coruña, Spain

    Rubén Varela-Calviño

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  1. Sandra Robla
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  2. Maruthi Prasanna
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  3. Rubén Varela-Calviño
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  4. Cyrille Grandjean
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  5. Noemi Csaba
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Contributions

Sandra Robla was in charge of the overall experimental execution, data analysis, writing, and figure preparation. Maruthi Prasanna contributed to the experimental execution and writing. Cyrille Grandjean was involved in the synthesis and characterization of the PsaA antigen, reviewing and editing the manuscript. R Varela-Calviño was involved in the design and supervision of the in vitro cell experiments, reviewing and editing the manuscript. Noemi Csaba was involved in writing, reviewing, editing, supervision, project design, and administration.

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Correspondence to Noemi Csaba.

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All procedures followed were in accordance with the ethical standards of the responsible institutional and national committees on human experimentation and with the Declaration of Helsinki. Informed consent was obtained from all patients for being included in the study.

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All institutional and national guidelines for the obtention and use of human blood were followed. Blood was drawn with the informed consent of all subjects and appropriate permission was obtained from the Institutional Ethics Committee (Comité Ético de Investigación Clínica de Galicia, CEIC). No animal or human studies were carried out by the authors for this article.

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Robla, S., Prasanna, M., Varela-Calviño, R. et al. A chitosan-based nanosystem as pneumococcal vaccine delivery platform. Drug Deliv. and Transl. Res. 11, 581–597 (2021). https://doi.org/10.1007/s13346-021-00928-3

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