Abstract
Avian pathogenic Escherichia coli (APEC) infection in poultry causes enormous economic losses and public health risks. Bacterial outer membrane vesicles (OMVs) and nano-sized proteolipids enriched with various immunogenic molecules have gained extensive interest as novel nanovaccines against bacterial infections. In this study, after the preparation of APEC O2-derived OMVs (APEC_OMVs) using the ultracentrifugation method and characterization of them using electron microscopy and nanoparticle tracking analyses, we examined the safety and vaccination effect of APEC_OMVs in broiler chicks and investigated the underlying immunological mechanism of protection. The results showed that APEC_OMVs had membrane-enclosed structures with an average diameter of 89 nm. Vaccination with 50 μg of APEC_OMVs had no side effects and efficiently protected chicks against homologous infection. APEC_OMVs could be effectively taken up by chicken macrophages and activated innate immune responses in macrophages in vitro. APEC_OMV vaccination significantly improved activities of serum non-specific immune factors, enhanced the specific antibody response and promoted the proliferation of splenic and peripheral blood lymphocytes in response to mitogen. Furthermore, APEC_OMVs also elicited a predominantly IFN-γ-mediated Th1 response in splenic lymphocytes. Our data revealed the involvement of both non-specific immune responses and specific antibody and cytokine responses in the APEC_OMV-mediated protection, providing broader knowledge for the development of multivalent APEC_OMV-based nanovaccine with high safety and efficacy in the future.
Highlights
Avian pathogenic Escherichia coli (APEC) is one of the major pathogens that have been recognized as serious threats to the global poultry industry [1,2,3]
APEC_OMVs were obtained from the culture supernatant of APEC O2 strain using a series of centrifugation procedures and purified using the density gradient centrifugation method
The results showed that these vesicles were intact nanosized structures with spherical morphology, and the majority of these nanovesicles ranged from 50 to 150 nm in diameter
Summary
Avian pathogenic Escherichia coli (APEC) is one of the major pathogens that have been recognized as serious threats to the global poultry industry [1,2,3]. APEC causes a variety of local and systemic diseases in many avian species, such as colibacillosis in broiler chickens [2,4]. Antibiotic regimens are used as a common measure to control APEC. The prevalence of multidrug-resistant APEC caused by the extensive usage of antibiotics has attracted significant concerns. Drug residues and transfers of resistant genes through poultry products are becoming severe threats to public health [7]. The use of effective vaccines is recognized as an important way to control APEC infections in today’s large-scale poultry industry [8,9]
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