Rectal and Intranasal Immunizations with Recombinant Urease Induce Distinct Local and Serum Immune Responses in Mice and Protect against Helicobacter pylori Infection

Abstract

To determine the optimal inductive sites for immunization againstHelicobacter pylori infection, the protective efficacy of recombinant urease (rUre) was assessed for mice given the vaccine by either the oral (p.o.), intranasal (i.n.), or rectal route. When mice were immunized with rUre (25 μg p.o. or rectally or 10 μg i.n.) plus heat-labile toxin from Escherichia coli as the mucosal adjuvant, all routes afforded protection against challenge withH. pylori, as indicated by a significant reduction in gastric urease activity (P < 0.0005) compared to that of sham-immunized controls. Quantitative H. pylori culture of stomach tissue demonstrated a >97% reduction in bacterial burden in mice immunized by all routes (P < 0.05). Induction of antiurease immunoglobulin A (IgA) levels in gastric luminal secretions after p.o. immunization was greater than after i.n. administration (means, 6.0 and 1.02 ng/ml, respectively) and was dependent upon challenge with H. pylori. However, immunization by the rectal route resulted in the generation of the highest levels of gastric antiurease IgA (mean, 40.89 ng/ml), which was detectable prior to challenge with H. pylori. Immunohistochemical staining of stomach tissue for cells secreting urease-specific antibody and CD4+ T cells showed levels of recruitment to be dependent upon challenge with H. pyloriand equivalent for all routes. These results identify both the rectum and nasal passages as suitable inductive sites for urease immunization.

The Adjuvant Effect of CpG Oligodeoxynucleotide Linked to the Non‐Toxic B Subunit of Cholera Toxin for Induction of Immunity Against H. pylori in Mice

“…Our studies confirm previous reports made by others that i.n. immunization of mice with antigen and an appropriate adjuvant can give rise to humoral and cellular immune responses in the gastroin-testinal tract mucosa [22,42,43]. Further, our finding on the failure of CTB as an effective nasal adjuvant for induction of immune response in the murine gastrointestinal tract is in line with the previous reports that i.n.…”

Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates

“…For this reason, mouse infection models that use highly host-adapted H. pylori strains may not be appropriate for vaccination studies. Indeed, it is perhaps significant that workers using these models have been unable to reproduce the levels of protection for single antigen preparations as seen in other Helicobacter infection models (Kleanthous et al, 1998;Keenan et al, 2000). In agreement with this, it was shown recently that 'sterilizing immunity' could only be achieved in H. pylori mouse models that used cag + strains as the challenge inoculum (Kleanthous et al, 2001).…”

“…At least 10 H. pylori mouse-colonizing strains have been reported in the literature (Marchetti et al, 1995;Lee et al, 1997;Guruge et al, 1998;Kleanthous et al, 1998;van Doorn et al, 1999;Janvier et al, 1999). Among these mouse-colonizing strains, four were shown to have a cagA + genotype (Marchetti et al, 1995;Lee et al, 1997;Guruge et al, 1998;van Doorn et al, 1999;Janvier et al, 1999).…”

Protection Against Helicobacter pylori Infection in Mongolian Gerbil by Intragastric or Intramuscular Administration of H. pylori Multicomponent Vaccine

“…Although we did not assess all the combinations of the H. pylori vaccine, this study implies that multicomponent vaccines are an important strategy for the development of H. pylori vaccine. Vaccine studies in animal models and human volunteers indicate that the adjuvant and route of administration play a crucial role in the induction of protective immune response [6,[20][21][22][23][24]. It is known that Al(OH) 3 is already approved for use as an adjuvant in humans because of its safety and stability.…”