TY - JOUR
T1 - Immunogenicity and protective efficacy of mucosal delivery of recombinant hcp of Campylobacter jejuni Type VI secretion system (T6SS)in chickens
AU - Singh, Ankita
AU - Nisaa, Khairun
AU - Bhattacharyya, Sudipta
AU - Mallick, Amirul Islam
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/7
Y1 - 2019/7
N2 - The type VI secretion system (T6SS)has recently emerged as a new pattern of protein secretions in Campylobacter jejuni (C. jejuni). Within the T6SS cluster, hemolysin co-regulated protein (hcp)is considered as a hallmark of functional T6SS and holds key role in bacterial virulence. As poultry is the primary reservoir of C. jejuni and the major sources for human infection, we evaluated the capacity of recombinant hcp (rhcp)immunization in blocking C. jejuni colonization in chickens with an aim to control bacterial transmission to humans via poultry food chain. Considering the mucosal route is the primary portal for C. jejuni entry and gut mucosa offers the apposite site for C. jejuni adherence, we investigated the immune-protective potential of intra-gastric administration of rhcp using chitosan-based nanoparticles. To achieve this goal, full length coding sequence of hcp gene from C. jejuni was cloned and expressed in E. coli. Purified rhcp was entrapped in chitosan-Sodium tripolyphosphate nanoparticles (CS-TPP NPs)and orally gavaged in chickens. Our results suggest that intra-gastric immunization of CS-TPP-rhcp induces consistent and steady increase in intestinal (sIgA)and systemic antibody (IgY)response against rhcp with significant reduction in cecal load of C. jejuni. The protection afforded by rhcp associated cellular responses with Th1 and Th17 profile in terms of increased expression of NFkB, IL-1β, IL-8, IL-6, IFN-γ and IL-17 A genes. Though systemic immunization of rhcp with IFA resulting in a robust systemic (IgY)and local (sIgA)antibody response, mucosal administration of rhcp loaded CS-TPP NPs was found to be superior in terms of bacterial clearance. Altogether, present study suggests that chitosan based intra-gastric delivery of rhcp have several advantages over the injectable composition and could be a promising vaccine approach to effectively control C. jejuni colonization in chickens.
AB - The type VI secretion system (T6SS)has recently emerged as a new pattern of protein secretions in Campylobacter jejuni (C. jejuni). Within the T6SS cluster, hemolysin co-regulated protein (hcp)is considered as a hallmark of functional T6SS and holds key role in bacterial virulence. As poultry is the primary reservoir of C. jejuni and the major sources for human infection, we evaluated the capacity of recombinant hcp (rhcp)immunization in blocking C. jejuni colonization in chickens with an aim to control bacterial transmission to humans via poultry food chain. Considering the mucosal route is the primary portal for C. jejuni entry and gut mucosa offers the apposite site for C. jejuni adherence, we investigated the immune-protective potential of intra-gastric administration of rhcp using chitosan-based nanoparticles. To achieve this goal, full length coding sequence of hcp gene from C. jejuni was cloned and expressed in E. coli. Purified rhcp was entrapped in chitosan-Sodium tripolyphosphate nanoparticles (CS-TPP NPs)and orally gavaged in chickens. Our results suggest that intra-gastric immunization of CS-TPP-rhcp induces consistent and steady increase in intestinal (sIgA)and systemic antibody (IgY)response against rhcp with significant reduction in cecal load of C. jejuni. The protection afforded by rhcp associated cellular responses with Th1 and Th17 profile in terms of increased expression of NFkB, IL-1β, IL-8, IL-6, IFN-γ and IL-17 A genes. Though systemic immunization of rhcp with IFA resulting in a robust systemic (IgY)and local (sIgA)antibody response, mucosal administration of rhcp loaded CS-TPP NPs was found to be superior in terms of bacterial clearance. Altogether, present study suggests that chitosan based intra-gastric delivery of rhcp have several advantages over the injectable composition and could be a promising vaccine approach to effectively control C. jejuni colonization in chickens.
KW - Campylobacter jejuni
KW - Chickens
KW - Chitosan nanoparticles
KW - Hemolysin co-regulated protein
KW - Mucosal immunity
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U2 - 10.1016/j.molimm.2019.04.016
DO - 10.1016/j.molimm.2019.04.016
M3 - Article
C2 - 31078054
AN - SCOPUS:85065186904
SN - 0161-5890
VL - 111
SP - 182
EP - 197
JO - Molecular Immunology
JF - Molecular Immunology
ER -