Biotechnology Letters

, Volume 41, Issue 12, pp 1415–1421 | Cite as

A food-grade engineered Lactococcus lactis strain delivering Helicobacter pylori Lpp20 alleviates bacterial infection in H. pylori-challenged mice

  • Nan Sun
  • Rongguang ZhangEmail author
  • Guangcai Duan
  • Xiaoyan Peng
  • Chen Wang
  • Shuaiyin Chen
  • Qingtang Fan
Original Research Paper



To construct a food-grade bacterium producing and delivering H. pylori Lpp20 antigen and evaluate its immune efficacy against H. pylori challenges with aim to develop anti-H. pylori oral vaccines and functional foods.


Lpp20 was expressed as a 22 kDa protein in Lactococcus lactis, constituting 11.2% of the cell lysate proteins, and recognized by mouse antisera. Mice orally gavaged with the engineered bacterium had elevated serum IgG levels and lowered urease activity of stomach following H. pylori challenges.


This study firstly reports a food-grade L. lactis strain delivering Lpp20 to mucosal immunization sites, demonstrating a novel efficient production and safe utilization mode of Lpp20, offering a promising vaccine candidate and health food sources.


Food-grade bacterium Functional food Genetically engineering Helicobacter pylori Lactococcus lactis Oral vaccination 



This work was supported by the National Natural Science Foundation of China (81773495) and National Science and Technology Major Program of China (2018ZX10301407).

Supporting information

Supplementary Table 1 Bacteria and plasmid vectors used herein.

Author contributions

NS, RZ and GD designed the project and wrote the manuscript. NS, XP and CW engineered the L. lactis strain and carried out the westernblot analysis and animal experimentation. SC and QF performed data analysis and conducted animal experiments.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests.

Supplementary material

10529_2019_2740_MOESM1_ESM.pdf (61 kb)
Supplementary material 1 (PDF 61 kb)


  1. Abdoh Q, Kharraz L, Ayoub K et al (2018) Helicobacter pylori resistance to antibiotics at the An-Najah National University Hospital: a cross-sectional study. Lancet 391(Suppl 2):S32CrossRefGoogle Scholar
  2. Chen S, Zhang R, Duan G, Shi J (2011) Food-grade expression of Helicobacter pylori ureB subunit in Lactococcus lactis and its immunoreactivity. Curr Microbiol 62:1726–1731CrossRefGoogle Scholar
  3. Gu Q, Song D, Zhu M (2009) Oral vaccination of mice against Helicobacter pylori with recombinant Lactococcus lactis expressing urease subunit B. FEMS Immunol Med Microbiol 56:197–203CrossRefGoogle Scholar
  4. Lee MH, Roussel Y, Wilks M, Tabaqchali S (2001) Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H. pylori infection in mice. Vaccine 19:3927–3935CrossRefGoogle Scholar
  5. Li X, Xing Y, Guo L, Lv X, Song H, Xi T (2014) Oral immunization with recombinant Lactococcus lactis delivering a multi-epitope antigen CTB-UE attenuates Helicobacter pylori infection in mice. Pathog Dis 72:78–86CrossRefGoogle Scholar
  6. Li Y, Chen Z, Ye J et al (2016) Antibody production and Th1-biased response induced by an epitope vaccine composed of cholera toxin B unit and Helicobacter pylori Lpp20 epitopes. Helicobacter 21:234–248CrossRefGoogle Scholar
  7. Liu W, Tan Z, Xue J et al (2016) Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection. Appl Microbiol Biotechnol 100:6219–6229CrossRefGoogle Scholar
  8. Ma YJ, Duan GC, Zhang RG, Fan QT, Zhang WD (2010) Mutation of iceA in Helicobacter pylori compromised IL-8 induction from human gastric epithelial cells. J Basic Microbiol 50(Suppl 1):S83–S88CrossRefGoogle Scholar
  9. Peng X, Zhang R, Duan G et al (2018) Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity. Sci Rep 8:6435CrossRefGoogle Scholar
  10. Sun N, Zhang R, Duan G et al (2017) An engineered food-grade Lactococcus lactis strain for production and delivery of heat-labile enterotoxin B subunit to mucosal sites. BMC Biotechnol 17:25CrossRefGoogle Scholar
  11. Zhang XJ, Feng SY, Li ZT, Feng YM (2015) Expression of Helicobacter pylori hspA gene in Lactococcus lactis NICE system and experimental study on its immunoreactivity. Gastroenterol Res Pract 2015:750932PubMedPubMedCentralGoogle Scholar
  12. Zhang R, Duan G, Shi Q et al (2016a) Construction of a recombinant Lactococcus lactis strain expressing a fusion protein of Omp22 and HpaA from Helicobacter pylori for oral vaccine development. Biotechnol Lett 38:1911–1916CrossRefGoogle Scholar
  13. Zhang R, Peng X, Duan G et al (2016b) An engineered Lactococcus lactis strain exerts significant immune responses through efficient expression and delivery of Helicobacter pylori Lpp20 antigen. Biotechnol Lett 38:2169–2175CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Nan Sun
    • 1
  • Rongguang Zhang
    • 1
    Email author
  • Guangcai Duan
    • 1
  • Xiaoyan Peng
    • 1
  • Chen Wang
    • 1
  • Shuaiyin Chen
    • 1
  • Qingtang Fan
    • 1
  1. 1.Department of Epidemiology and Statistics, College of Public HealthZhengzhou UniversityZhengzhouChina

Personalised recommendations