Nasal immunization with mannan-decorated mucoadhesive HPMCP microspheres containing ApxIIA toxin induces protective immunity against challenge infection with Actinobacillus pleuropneumoiae in mice
| Autor: | Bijay Singh, Hui-Shan Li, Chong-Su Cho, Zhong-Shan Hong, Han Sang Yoo, Yun-Jaie Choi, Tae-Eun Park, Min-Kyoung Shin, Sushila Maharjan, Sang-Kee Kang |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Pharmaceutical Science Antigen-Presenting Cells Respiratory Mucosa Methylcellulose Microbiology Cell Line Mannans 03 medical and health sciences Hemolysin Proteins Mice Immune system Actinobacillus Infections Antigen Bacterial Proteins medicine Animals Sulfhydryl Compounds Antigen-presenting cell Actinobacillus pleuropneumoniae Immunity Mucosal Administration Intranasal Mice Inbred BALB C biology Immunogenicity Adhesiveness biology.organism_classification Antibodies Bacterial Microspheres Immunoglobulin A Vaccination 030104 developmental biology Immunoglobulin G Immunology Bacterial Vaccines Nasal administration Female Immunization Adjuvant Bronchoalveolar Lavage Fluid |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 233 |
| ISSN: | 1873-4995 |
| Popis: | The development of subunit mucosal vaccines requires an appropriate delivery system or an immune modulator such as an adjuvant to improve antigen immunogenicity. The nasal route for vaccine delivery by microparticles has attracted considerable interest, although challenges such as the rapid mucociliary clearance in the respiratory mucosa and the low immunogenicity of subunit vaccine still remain. Here, we aimed to develop mannan-decorated mucoadhesive thiolated hydroxypropylmethyl cellulose phthalate (HPMCP) microspheres (Man-THM) that contain ApxIIA subunit vaccine - an exotoxin fragment as a candidate for a subunit nasal vaccine against Actinobacillus pleuropneumoniae. For adjuvant activity, mucoadhesive thiolated HPMCP microspheres decorated with mannan could be targeted to the PRRs (pathogen recognition receptors) and mannose receptors (MR) of antigen presenting cells (APCs) in the respiratory immune system. The potential adjuvant ability of Man-THM for intranasal immunization was confirmed by in vitro and in vivo experiments. In a mechanistic study using APCs in vitro, it was found that Man-THM enhanced receptor-mediated endocytosis by stimulating the MR of APCs. In vivo, the nasal vaccination of ApxIIA-loaded Man-THM in mice resulted in higher levels of mucosal sIgA and serum IgG than mice in the ApxIIA and ApxIIA-loaded THM groups due to the specific recognition of the mannan in the Man-THM by the MRs of the APCs. Moreover, ApxIIA-containing Man-THM protected immunized mice when challenged with strains of A. pleuropneumoniae serotype 5. These results suggest that mucoadhesive Man-THM may be a promising candidate for a nasal vaccine delivery system to elicit systemic and mucosal immunity that can protect from pathogenic bacteria infection. |
| Databáze: | OpenAIRE |
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