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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1490003
This article is part of the Research Topic Community Series in Research Advances of Tuberculosis Vaccine and its Implication on COVID-19: Volume III View all articles

Enhancing Cell-Mediated Immunity through Dendritic Cell Activation: The Role of Tri-GalNAc-Modified PLGA-PEG Nanoparticles Encapsulating SR717

Provisionally accepted
Yang Gong Yang Gong Hongbin Jia Hongbin Jia Wenrui Dang Wenrui Dang Ting Zhou Ting Zhou Pu He Pu He Xiaolei Wang Xiaolei Wang *Bingdong Zhu Bingdong Zhu *
  • Lanzhou University, Lanzhou, China

The final, formatted version of the article will be published soon.

    Objective: Vaccines against intracellular pathogens like Mycobacterium tuberculosis (M. tuberculosis) require the induction of effective cell-mediated immunity.This study is to develop an adjuvant targeted to dendritic cells (DCs), one of the main antigen-presenting cells (APCs), so as to assist in inducing a long-term cellular immune response to M. tuberculosis protein antigens. Methods: Polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) modified with Triantennary N-Acetylgalactosamine (Tri-GalNAc) were prepared to target DCs. Additionally, the stimulator of interferon genes (STING) agonist SR717 was encapsulated within PLGA-PEG NPs to activate DCs. Meanwhile, M. tuberculosis fusion protein (TP) was encapsulated in PLGA-PEG NPs to construct vaccine candidates: TP/Tri-GalNAc-PLGA-PEG-SR717 (TP/GPS in short) and TP/ Tri-GalNAc-PLGA-PEG (TP/GP in short). The targeting and activation effects of these NPs were assessed in vitro and in vivo, and their immunogenicity were evaluated in mice. Results: Tri-GalNAc modification significantly enhanced the targeting of NPs to DCs, and encapsulated SR717 effectively promoted the maturation and activation of DCs. TP/GPS elicited a potent antigen-specific T cell immune response and successfully induced long-term immune memory in mice. Moreover, after the mice were infected with H37Ra via nasal instillation, TP/GPS significantly reduced the bacterial load in their lungs. Conclusion: Tri-GalNAc-modified PLGA-PEG NPs in combination with SR717 targeted and activated DCs, effectively assisting M. tuberculosis antigen in inducing long-term T cell-mediated immunity. This approach offers an innovative and effective adjuvant strategy for the development of subunit vaccine against intracellular pathogen.

    Keywords: adjuvant, Dendritic Cells, Tri-GalNAc, SR717, PLGA-PEG nanoparticles, Tuberculosis

    Received: 02 Sep 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Gong, Jia, Dang, Zhou, He, Wang and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiaolei Wang, Lanzhou University, Lanzhou, China
    Bingdong Zhu, Lanzhou University, Lanzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.