Author/Authors :
Liang ، Zhengmin Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Li ، Miaoxuan Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Ni ، Jiamin Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Hussain ، Tariq Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Yao ، Jiao Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Song ، Yinjuan Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Liu ، Yiduo Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Wang ، Haoran Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University , Zhou ، Xiangmei Key Laboratory of Animal Epidemiology and Zoonosis, National Animal Transmissible Spongiform Encephalopathy Laboratory - College of Veterinary Medicine - Ministry of Agriculture, China Agricultural University
Abstract :
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 PLGAbased 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.
Keywords :
PLGA , Nanoparticles , CFP10 , Mycobacterium bovis , Mucosal immunization
