An engineered food-grade Lactococcus lactis strain for production and delivery of heat-labile enterotoxin B subunit to mucosal sites.

Authors:
Nan Sun
Nan Sun
Zhejiang University of Technology
China
Rongguang Zhang
Rongguang Zhang
Institute of Biophysics
China
Guangcai Duan
Guangcai Duan
Zhengzhou University
China
Xiaoyan Peng
Xiaoyan Peng
Beijing Institute of Ophthalmology
United States
Chen Wang
Chen Wang
Mayo Clinic
Phoenix | United States
Qingtang Fan
Qingtang Fan
College of Public Health
Shuaiyin Chen
Shuaiyin Chen
Zhengzhou University
China
Yuanlin Xi
Yuanlin Xi
College of Public Health
Iowa City | United States

BMC Biotechnol 2017 03 6;17(1):25. Epub 2017 Mar 6.

Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.

Background: Recent researches have been focusing on mucosal immune adjuvants, which play the key roles in mucosal immunization and have become the limitation for non-injected vaccine development. Escherichia coli heat-labile enterotoxin B subunit (LTB) was regarded as a promising mucosal adjuvant for its nontoxicity and potent activity. LTB preparation issues have always been recurring, in part owing to that the recombinant LTB expressed by E. coli does not act as its native form.

Results: We constructed an engineered Lactococcus lactis strain using a food-grade expression system. The LTB secreted by the engineered strain was detected in the culture supernatant, constituting 10.3% of the supernatant proteins, and recognized by mouse anti-LTB antibodies. The engineered strain, co-administered orally to SPF BALB/c mice with a H. pylori vaccine candidate expressing Lpp20 antigen, could significantly enhance the Lpp20-induced mucosal SIgA antibody responses against H. pylori.

Conclusions: This is the first report that LTB was efficiently produced and delivered via using a food-grade lactococcal expression system, which offers a novel production and utilization mode of this crucial mucosal adjuvant. The engineered L. lactis strain secreting LTB has considerable potential for oral vaccine formulation owing to its outstanding safety, adjuvant activity and high-level production.

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http://dx.doi.org/10.1186/s12896-017-0345-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339977PMC
March 2017
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