TY - JOUR
T1 - Mucosal delivery of live Lactococcus lactis expressing functionally active JlpA antigen induces potent local immune response and prevent enteric colonization of Campylobacter jejuni in chickens
AU - Gorain, Chandan
AU - Singh, Ankita
AU - Bhattacharyya, Sudipta
AU - Kundu, Anirban
AU - Lahiri, Aritraa
AU - Gupta, Subhadeep
AU - Mallick, Amirul I.
N1 - Funding Information:
We thank Prof. Luis G Bermúdez-Humarán of French National Institute for Agricultural Research, Paris, France, for providing pNZ8048 derived plasmid backbone and his valuable suggestion to establish L. lactis in our lab. We acknowledge Dr. Peter Le, Sunnybrook Research Institute, University of Toronto for his help in plasmid construction and Dr. Asish Kumar Mukhopadhyay, Scientist F, NICED (ICMR), Kolkata, India for providing us human clinical isolate of C. jejuni (BCH71). We acknowledge Mr. Avinash Sharma, a former MS student in our lab, for cloning of JlpA gene in E. coli. We would like to thank DST-FIST Transmission Electron Microscope (TEM) Facility and Central Imaging Facility of IISER Kolkata. This work was supported by a grant from Department of Biotechnology, Ministry of Science & Technology, Govt of India (Grant No. BT/PR21437/ADV/90/248/2016).
Funding Information:
We thank Prof. Luis G Bermúdez-Humarán of French National Institute for Agricultural Research, Paris, France, for providing pNZ8048 derived plasmid backbone and his valuable suggestion to establish L. lactis in our lab. We acknowledge Dr. Peter Le, Sunnybrook Research Institute, University of Toronto for his help in plasmid construction and Dr. Asish Kumar Mukhopadhyay, Scientist F, NICED (ICMR), Kolkata, India for providing us human clinical isolate of C. jejuni (BCH71). We acknowledge Mr. Avinash Sharma, a former MS student in our lab, for cloning of JlpA gene in E. coli. We would like to thank DST-FIST Transmission Electron Microscope (TEM) Facility and Central Imaging Facility of IISER Kolkata. This work was supported by a grant from Department of Biotechnology, Ministry of Science & Technology, Govt of India (Grant No. BT/PR21437/ADV/90/248/2016).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2020/2/11
Y1 - 2020/2/11
N2 - Successful colonization of the mucosal epithelial cells is the key early step for Campylobacter jejuni (C. jejuni) pathogenesis in humans. A set of Surface Exposed Colonization Proteins (SECPs) are known to take leading role in bacterial adhesion and subsequent host pathogenesis. Among the major SECPs, the constitutively expressed C. jejuni surface lipoprotein Jejuni lipoprotein A (JlpA), interacts with intestinal heat shock protein 90α (Hsp90α) and contributes in disease progression by triggering pro-inflammatory responses via activation of NF-κB and p38 MAP kinase pathways. In addition to its ability to express on the surface, high sequence conservation of JlpA protein among different Campylobacter spp make it a suitable vaccine target against C. jejuni. Given that chickens are the primary source for C. jejuni infection in humans and persistent cecal colonization significantly contribute in pathogen transmission, we explicitly used chickens as a model to test the immune-protective efficacy of JlpA protein. Taking into account that gastro-intestinal tract is the major site for C. jejuni colonization, we chose to use mucosal (intragastric) route as mode for JlpA antigen delivery. To deliver JlpA via mucosal route, we engineered a food grade Lactic acid producing bacteria, Lactococcus lactis (L. lactis) to express functionally active JlpA protein in the surface. Further, we demonstrated its ability to substantially improve the antigen specific local immune responses in the intestine along with significant immune-protection against enteric colonization of C. jejuni in chickens.
AB - Successful colonization of the mucosal epithelial cells is the key early step for Campylobacter jejuni (C. jejuni) pathogenesis in humans. A set of Surface Exposed Colonization Proteins (SECPs) are known to take leading role in bacterial adhesion and subsequent host pathogenesis. Among the major SECPs, the constitutively expressed C. jejuni surface lipoprotein Jejuni lipoprotein A (JlpA), interacts with intestinal heat shock protein 90α (Hsp90α) and contributes in disease progression by triggering pro-inflammatory responses via activation of NF-κB and p38 MAP kinase pathways. In addition to its ability to express on the surface, high sequence conservation of JlpA protein among different Campylobacter spp make it a suitable vaccine target against C. jejuni. Given that chickens are the primary source for C. jejuni infection in humans and persistent cecal colonization significantly contribute in pathogen transmission, we explicitly used chickens as a model to test the immune-protective efficacy of JlpA protein. Taking into account that gastro-intestinal tract is the major site for C. jejuni colonization, we chose to use mucosal (intragastric) route as mode for JlpA antigen delivery. To deliver JlpA via mucosal route, we engineered a food grade Lactic acid producing bacteria, Lactococcus lactis (L. lactis) to express functionally active JlpA protein in the surface. Further, we demonstrated its ability to substantially improve the antigen specific local immune responses in the intestine along with significant immune-protection against enteric colonization of C. jejuni in chickens.
KW - Campylobacter jejuni
KW - Enteric colonization
KW - JlpA
KW - Lactococcus lactis
KW - Mucosal immune response
UR - http://www.scopus.com/inward/record.url?scp=85077708882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077708882&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2019.12.064
DO - 10.1016/j.vaccine.2019.12.064
M3 - Article
C2 - 31932136
AN - SCOPUS:85077708882
SN - 0264-410X
VL - 38
SP - 1630
EP - 1642
JO - Vaccine
JF - Vaccine
IS - 7
ER -