Protective Efficacy of Anti-HelicobacterpyloriImmunity following Systemic Immunization of Neonatal Mice

Abstract

Helicobacter pylori infection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H. pylori immunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectious H. pylori when the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection of H. pylori.

Current Status and Prospects for a Helicobacter pylori Vaccine

“…28,30 Perhaps most surprising has been the observation that protective immunity equivalent to orogastric delivery can be induced through the use of systemic routes, including subcutaneous and intraperitoneal. [32][33][34] These results are in contrast to the failure of systemic immunization to protect against other mucosal pathogens but have been the impetus for at least 1 phase 3 clinical trial using parenteral immunization described later. 35 Second, protection in mice can be achieved using numerous distinct H pylori protein antigens.…”

“…49 Lastly, prophylactic immunization against H pylori is effective when administered to neonatal mice. 32 This experiment has important implications if a vaccine is to be administered to humans at an early age. Although there may be utility in administering a therapeutic vaccine to the adult population in countries where H pylori-associated gastric cancer remains prevalent, a more effective strategy for long-term reductions in H pylori infections and associated pathology may be to immunize children because most infections occur in early childhood.…”

Th immune response induced byH pylorivaccine with chitosan as adjuvant and its relation to immune protection

“…Gottweln et al reported that the two kinds of H pylori vaccine with complete Freund's or aluminum as adjuvant, which induce Th1 and Th2 immune response respectively, could induce protective immune response in vivo in mice, indicating that Th1 and Th2 immune response have the effect of immune protection. Eisenberg et al [21] immunized neonatal and adult mice with H pylori antigen and complete or incomplete Freund's adjuvant and found that the number of T cells producing Th1 cytokines like IFN-γ, IL-2 and Th2 cytokines like IL-4 IL-5 increased, have the effect of immune protection. Sommer et al [22] used CpG oligonucleotide as adjuvant to induce Th1 immune response, and found that it could not protect against H pylori infection but lead to more serious gastritis.…”

<italic>Helicobacter pylori </italic>Infection: Regulatory T Cells and Their Participation in the Immune Response

“…Investigations have shown shown that TGF-β acts inhibited the secretion of pro-inflammatory cytokines: Th1 and Th17. "Knockout" mice for TGF-β develop a deadly generalized inflammation (50). Study has demonstrated that the naïve CD4+ T cell development into Treg was enhanced in the presence of GECs (Gastric Epithelial Cells) derived TGF-β.…”