title: Heterologous expression of carcinoembryonic antigen in Lactococcus lactis via LcsB-mediated surface displaying system for oral vaccine development.
abstract: OBJECTIVE
  Carcinoembryonic antigen (CEA) is an attractive target for immunotherapy because it is expressed minimally in normal tissue, but is overexpressed in a wide variety of malignant epithelial tissues. Lactic acid bacteria (LABs), widely used in food processes, are attractive candidates for oral vaccination. Thus, we examined whether LABs could be used as a live vaccine vector to deliver CEA antigen.
  
  
  METHODS
  CEA was cloned into an Escherichia coli/Lactococcus lactis shuttle vector pSEC:LEISS under the control of a nisin promoter. For displaying the CEA on the cell surface of the L. lactis strain, the anchor motif LcsB from the S-layer protein of Lactobacillus crispatus was fused with CEA. Intracellular and cell surface expression of the CEA-LcsB fusion was confirmed by western blot analysis.
  
  
  RESULTS
  Significantly higher levels of CEA-specific secretory immunoglobulin A in the sera of mice were observed upon oral administration of strain cultures containing the CEA-LcsB fused protein. In addition, the CEA-LcsB antigen group showed a higher spleen index compared to the CEA antigen alone or negative control, demonstrating that surface-displayed CEA antigen could induce a higher immune response.
  
  
  CONCLUSIONS
  These results provided the first evidence for displaying CEA antigen on the cell surfaces of LABs as oral vaccines against cancer or infectious diseases.
authors: Health Science Exchange and Service Center of Jinan, Jinan 250013, China. Electronic address: 1316527255@qq.com.
authors: Xiaowei
authors: X
authors: Zhang
authors: State Key Laboratory of Biological Fermentation Engineering of Beer, Tsingtao Brewery Co. Ltd., Qingdao, China; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors: Shumin
authors: S
authors: Hu
authors: Health Science Exchange and Service Center of Jinan, Jinan 250013, China.
authors: Xue
authors: X
authors: Du
authors: Health Science Exchange and Service Center of Jinan, Jinan 250013, China.
authors: Tiejun
authors: T
authors: Li
authors: State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors: Lanlan
authors: L
authors: Han
authors: State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China. Electronic address: kongjian@sdu.edu.cn.
authors: Jian
authors: J
authors: Kong
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D013294:Lactococcus lactis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D007070:Immunoglobulin A
keywords: Lactococcus lactis; S-layer; carcinoembryonic antigen; gene expression