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Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity

  • Biotechnological products and process engineering
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Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that localizes to and colonizes mucosal tissue. Thus, vaccines that elicit a strong mucosal response against P. aeruginosa should be superior to other vaccination strategies. In this study, to stimulate rapid and enhanced mucosal immune responses, mannose-modified chitosan microspheres loaded with the recombinant outer membrane protein OprF190–342-OprI21–83 (FI) (FI-MCS-MPs) of P. aeruginosa were developed as a potent subunit vaccine for mucosal delivery. FI-MCS-MPs were successfully obtained via the tripolyphosphate ionic crosslinking method. Confocal and immunohistochemical analyses indicated that FI-MCS-MPs exhibited the ability to bind the macrophage mannose receptor (MMR, CD206) in vitro and in vivo. After intranasal immunization of mice with FI-MCS-MPs, FI-specific humoral immune responses were detected, measured as local IgM antibody titers in lung tissue slurry; IgA antibody titers in nasal washes, bronchoalveolar lavage (BAL), and intestinal lavage; and systemic IgA and IgG antibody titers in serum. FI-MCS-MPs induced early and high mucosal and systemic humoral antibody responses comparable to those in the group vaccinated with unmodified mannose. High levels of IFN-γ and IL-4 in addition to T lymphocyte subsets induced a mixed Th1/Th2 response in mice immunized with FI-MCS-MPs, resulting in the establishment of cellular immunity. Additionally, when immunized mice were challenged with P. aeruginosa via the nasal cavity, FI-MCS-MPs demonstrated 75 % protective efficacy. Together, these data indicate that mannose-modified chitosan microspheres are a promising subunit delivery system for vaccines against P. aeruginosa infection.

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Acknowledgments

This study was supported by the National High Technology Research and Development Program of China (No. 2011AA10A210). The authors thank Ye Yuan for help with chemically synthesized statistical analysis.

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  1. College of Veterinary Medicine, Jilin University, Xi’an Road 5333#, Changchun, 130062, China

    Ziyin Cui, Dong Han, Xiaoyu Sun, Mingliang Zhang, Xin Feng, Changjiang Sun, Jingmin Gu, Chunyu Tong, Liancheng Lei & Wenyu Han

  2. Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, 225009, China

    Wenyu Han

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  1. Ziyin Cui
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Cui, Z., Han, D., Sun, X. et al. Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity. Appl Microbiol Biotechnol 99, 667–680 (2015). https://doi.org/10.1007/s00253-014-6147-z

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