Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity

Abstract

Helicobacter pylori neutrophil-activating protein A subunit (NapA) has been identified as a virulence factor, a protective antigen and a potent immunomodulator. NapA shows unique application potentials for anti-H. pylori vaccines and treatment strategies of certain allergic diseases and carcinomas. However, appropriate production and utilization modes of NapA still remain uncertain to date. This work has established a novel efficient production and utilization mode of NapA by using L. lactis as an expression host and delivery vector, and demonstrated immune protective efficacy and immune modulatory activity of the engineered L. lactis by oral vaccination of mice. It was observed for the first time that H. pylori NapA promotes both polarized Th17 and Th1 responses, which may greatly affect the clinical application of NapA. This report offers a promising anti-H. pylori oral vaccine candidate and a potent mucosal immune modulatory agent. Meanwhile, it uncovers a way to produce and deliver the oral vaccine and immunomodulator by fermentation of food like milk, which might have striking effects on control of H. pylori infection, gastrointestinal cancers, and Th2 bias allergic diseases, including many food allergies.

Review: Helicobacter: Inflammation, immunology, and vaccines

“…46 In a prophylactic vaccine study, however, mice given the L. lactis NapA preparation demonstrated only marginally lower levels of H pylori colonization, when compared with animals given either L. lactis vector alone or PBS. Vaccination with this strain promoted polarized Th17 and Th1 responses and induced post-immunization inflammation.…”

“…42 To overcome the harsh effects of the gastrointestinal tract on the immunogenicity of vaccine preparations, Liu et al 43 developed an approach based on the use of HP55/poly(n-butylcyanoacrylate) (PBCA) NPs to carry an H pylori subunit vaccine (CCF) for oral administration. 44,45 Peng et al 46 43 Oral vaccination of mice with HP55/PBCA-CCF NPs promoted the production of serum antigen-specific antibodies and secretory IgA, as well as pro-inflammatory cytokine production by splenic lymphocytes.…”

Helicobacter: Inflammation, immunology, and vaccines

“…As an alternative to classical vaccines, two groups engineered recombinant Lactococcus lactis strains to overexpress H. pylori antigens: (a) the complete H. pylori adhesin A (HpaA), a lipoprotein located in the cellular outer membrane and flagellum sheath, and (b) the neutrophil‐activating protein A subunit (NapA), a virulence factor that recruits and stimulates neutrophils and protects H. pylori against oxidative damage . Animals inoculated once a week for four weeks with the recombinant L. lactis strain developed anti‐HpaA and anti‐NapA IgG, and fecal IgA . The immunization with the NapA‐expressing L. lactis strain also initiated a Th1 and Th17 response by splenic cells under an antigenic recall assay using H. pylori lysates, a partial reduction in H. pylori colonization, but no significant change in the level of gastritis.…”

“…Animals inoculated once a week for four weeks with the recombinant L. lactis strain developed anti‐HpaA and anti‐NapA IgG, and fecal IgA . The immunization with the NapA‐expressing L. lactis strain also initiated a Th1 and Th17 response by splenic cells under an antigenic recall assay using H. pylori lysates, a partial reduction in H. pylori colonization, but no significant change in the level of gastritis. It would now be of interest to assess the role of the HpaA‐expressing strain on H. pylori colonization and clinical outcomes.…”

“…As an alternative to classical vaccines, two groups engineered recombinant Lactococcus lactis strains to overexpress H. pylori antigens: (a) the complete H. pylori adhesin A (HpaA), 42 a lipoprotein located in the cellular outer membrane and flagellum sheath, and (b) the neutrophil-activating protein A subunit (NapA), 43 a virulence factor that recruits and stimulates neutrophils and protects H. pylori against oxidative damage. 44 Animals inoculated once a week for four weeks with the recombinant L. lactis strain developed anti-HpaA and anti-NapA IgG, and fecal IgA.…”