title: An engineered food-grade Lactococcus lactis strain for production and delivery of heat-labile enterotoxin B subunit to mucosal sites.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.|Henan Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China. zrg@zzu.edu.cn.|Henan Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China. zrg@zzu.edu.cn.
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China. gcduan@zzu.edu.cn.|Henan Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China. gcduan@zzu.edu.cn.
authors.forename: Guangcai
authors.initials: G
authors.lastname: Duan
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Qingtang
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Shuaiyin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Xi
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines; D004768:Enterotoxins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D007778:Lactobacillus / Q000145:classification / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000276:immunology*; D019936:Probiotics; D015202:Protein Engineering / Q000379:methods*; D013045:Species Specificity; D013696:Temperature
chemical_list: D001428:Bacterial Vaccines; D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal
keywords: Food-grade; Helicobactor pylori; LTB; Lactococcus lactis; Lpp20; Oral vaccine