Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity.
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.
College of Veterinary Medicine, Jilin University, Xi'an Road 5333#, Changchun, 130062, People's Republic of China.
Ziyin
Z
Cui
Dong
D
Han
Xiaoyu
X
Sun
Mingliang
M
Zhang
Xin
X
Feng
Changjiang
C
Sun
Jingmin
J
Gu
Chunyu
C
Tong
Liancheng
L
Lei
Wenyu
W
Han
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood / Q000737:chemistry; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D008358:Mannose / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D008969:Molecular Sequence Data; D011552:Pseudomonas Infections / Q000276:immunology* / Q000517:prevention & control; D054406:Pseudomonas Vaccines / Q000737:chemistry / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; C547605:OprF protein, Pseudomonas aeruginosa; D054406:Pseudomonas Vaccines; D011994:Recombinant Proteins; C060507:outer membrane lipoprotein I, Bacteria; D015847:Interleukin-4; D007371:Interferon-gamma; D048271:Chitosan; D008358:Mannose