Tabriz University of Medical Sciences BioImpacts 2228-5652 12 5 2022 09 01 CFP10–loaded PLGA nanoparticles as a booster vaccine confer protective immunity against Mycobacterium bovis 395 404 10.34172/bi.2022.23645 EN Zhengmin Liang https://orcid.org/0000-0001-6473-4511 Miaoxuan Li Jiamin Ni Tariq Hussain Jiao Yao Yinjuan Song Yiduo Liu Haoran Wang Xiangmei Zhou https://orcid.org/0000-0003-1566-5745 Journal Article 10.34172/bi.2022.23645 2021 02 01 2021 10 20 Introduction: The limited efficacy of BCG (bacillus Calmette–Guérin) urgently requires new effective vaccination approaches for the control of tuberculosis. Poly lactic-co-glycolic acid (PLGA) is a prevalent drug delivery system. However, the effect of PLGA-based nanoparticles (NPs) against tuberculosis for the induction of mucosal immune response is no fully elucidated. In this study, we hypothesized that intranasal immunization with culture filtrate protein-10 (CFP10)-loaded PLGA NPs (CFP10-NPs) could boost the protective immunity of BCG against Mycobacterium bovis in mice. Methods: The recombinant protein CFP10 was encapsulated with PLGA NPs to prepare CFP10-NPs by the classical water–oil-water solvent-evaporation method. Then, the immunoregulatory effects of CFP10-NPs on macrophages in vitro and on BCG-immunized mice in vivo were investigated. Results: We used spherical CFP10-NPs with a negatively charged surface (zeta-potential −28.5 ± 1.7 mV) having a particle size of 281.7 ± 28.5 nm in diameter. Notably, CFP10-NPs significantly enhanced the secretion of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in J774A.1 macrophages. Moreover, mucosal immunization with CFP10-NPs significantly increased TNF-α and IL-1β production in serum, and immunoglobulin A (IgA) secretion in bronchoalveolar lavage fluid (BALF), and promoted the secretion of CFP10-specific interferon-γ (IFN-γ) in splenocytes of mice. Furthermore, CFP10-NPs immunization significantly reduced the inflammatory area and bacterial load in lung tissues at 3-week post-M. bovis challenge. Conclusion: CFP10-NPs markedly improve the immunogenicity and protective efficacy of BCG. Our findings explore the potential of the airway mucosal vaccine based on PLGA NPs as a vehicle for targeted lung delivery.