Coated nanoparticles enhance immune efficacy of Helicobacter pylori outer membrane vesicles by activating Th1/Th2/Th17 responses.

Abstract

Antibiotic resistance has emerged as a pressing global public health crisis. The development of a safe and efficient Helicobacter pylori vaccine has become an important measure to eradicate Hpylori infection. Outer membrane vesicles (OMVs) secreted by Gram-negative bacteria are immunogenic and have received increasing attention in the development of vaccines against bacterial infections. In this study, Hpylori was used as a model pathogen, Hpylori outer membrane vesicle (HM) as an antigen, and dendritic mesoporous organosilica nanoparticles (DMON) as a carrier to load lipopolysaccharide (LPS) as an adjuvant to obtain a stable LPS@DMON@HM vaccine. The nanovaccine markedly enhanced the phagocytosis of macrophages and the secretion of IL-4, IFN-gamma, and IL-17A in vitro. In vivo, LPS@DMON@HM can significantly increase the specific antibody titer, and the serum-specific IgG antibody titer after vaccine immunization can reach 1:12,800, which is 16 times that of free HM immunization. Further studies indicated that the levels of Th1, Th2, and Th17 cytokines in spleen cells were induced to show a marked elevation. The results showed that LPS@DMON@HM had stronger immunogenicity and induced higher levels of humoral immunity, mucosal immunity, and Th1/Th2/Th17 cellular immune responses compared with free HM. The vaccine exhibited no toxicity at the tested doses. This study establishes a mechanistic foundation for developing next-generation Hpylori vaccines with optimized safety-efficacy profiles and simultaneously offers a reference for the development of vaccines against other Gram-negative pathogens. SIGNIFICANCE STATEMENT: Infection with Helicobacter pylori is closely associated with a wide range of gastrointestinal diseases; however, antibiotic resistance has been significantly undermining its therapeutic efficacy. The LPS@DMON@HM nanovaccine developed in this study can induce high levels of anti-Hpylori IgG after immunization of mice and can also induce mucosal immunity and Th1/Th2/Th17 mixed immune responses. It is anticipated to be further investigated as a nonantibiotic therapeutic option for Hpylori infection.