Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA nanoparticles promote immune protection

Eur J Pharm Biopharm. 2017 Feb:111:33-43. doi: 10.1016/j.ejpb.2016.11.007. Epub 2016 Nov 16.

Abstract

Oral vaccination, is notoriously weak or nonimmunogenic. One of the major reasons is the inefficient antigen uptake caused by enzymolysis and hydrolysis in the gastrointestinal tract. In this study, acid-resistant HP55/PLGA nanoparticle was developed as an oral delivery system to protect H. pylori recombinant antigen CCF against the complex gastrointestinal environment. These ∼200nm particles controlled the release of antigen in the acidic environment (pH⩽5.5). Immunized mice with HP55/PLGA-CCF nanoparticles induced high levels of urease-specific antibodies and memory T cell responses. A month after H. pylori challenge, 43% of mice were completely protected. The protection was highly associated with the Th1/Th17-bias immune response, which had been recognized as an optimal immunity against H. pylori infection. In addition, a mass of T-cells were observed in the lamina propria of mice immunized with CCF, especially in the HP55/PLGA-CCF nanoparticles administered recipients, and contributed to the development of postimmunization gastritis. These results indicate that oral immunization with acid-resistant HP55/PLGA nanoparticles encapsulating vaccine antigens represent a promising strategy for antigen protection, slow-release and targeting, and thus prevented gastrointestinal infection.

Keywords: Gastritis; Helicobacter pylori; Mucosal immunity; Nanoparticles; Oral vaccine delivery system.

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Oral
  • Animals
  • Antibodies, Bacterial / immunology*
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines / administration & dosage*
  • Gastric Mucosa / metabolism
  • Gastritis / immunology
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / immunology*
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Lactic Acid / chemistry*
  • Lymphocytes / cytology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Real-Time Polymerase Chain Reaction

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Immunoglobulin A
  • Immunoglobulin G
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid