Replication-Defective Adenovirus Infection ReducesHelicobacter felisColonization in the Mouse in a Gamma Interferon- and Interleukin-12-Dependent Manner

Abstract

Helicobacter infection leads to chronic inflammation of the stomach. Although the infection persists in spite of an immune response, animal studies have shown that adjuvant-based oral vaccines can protect against infection and even eliminate established infection. These vaccines are thought to induce a Th2 immune response, counterbalancing the Th1 response seen with natural infections. As a prelude to using adenovirus vectors carrying cytokine genes to modulate the immune response to established Helicobacter felisinfection, we first examined the effect of the replication-defective adenovirus (RDA) vector itself. C57BL/6 mice chronically infected withH. felis (8 to 10 weeks) received intramuscular injections of RDA. The effect of RDA on the severity of H. feliscolonization and the degree of gastric inflammation was assessed 2 weeks later. RDA caused a significant decrease in H. feliscolonization without significantly altering the associated inflammation. RDA did not alter the H. felis-specific immunoglobulin G1 (IgG1), IgG2a, and IgA responses in the serum but was associated with an increase in gamma interferon (IFN-γ)-producing CD8+ spleen cells. To determine if IFN-γ or Th1 cytokines were involved in the response to RDA, we examined RDA treatment ofH. felis infection in mice lacking either IFN-γ or interleukin-12 (IL-12). RDA failed to alter H. feliscolonization in either of these two mouse strains. Thus, viral infection of mice chronically infected with H. felis led to a significant decrease in H. felis colonization in an IFN-γ- and IL-12-dependent manner. These results demonstrate that Th1 responses associated with systemic viral infection can influence an established H. felis infection.

Immunization with Attenuated Salmonella typhimurium Producing Catalase in Protection against Gastric Helicobacter pylori Infection in Mice

“…A similar result was obtained in their study; either poliovirus replicons alone or poliovirus replicons plus recombinant ureB could elicit a Th1-associated immune response [33]. Jiang et al found that the Th1 response associated with systemic replication-defective adenovirus infection could reduce Helicobacter felis colonization in mice [27]. Similarly to Jiang et al, we found that mice immunized with SL3261 alone were partially protected against H. pylori infection; even three mice in the SL3261 immunized group were protected.…”

Intranasal CpG‐Oligodeoxynucleotide is a Potent Adjuvant of Vaccine against Helicobacter pylori, and T Helper 1 Type Response and Interferon‐γ Correlate with the Protection

“…Immunostimulatory sequence CpG-oligodeoxynucleotides (CpG-ODN) have previously been shown to provide effective adjuvant activity for the induction of systemic Th1-biased immunity toward protein antigens coadministered via intradermal and intramuscular routes. The immune response includes the induction of a Th1 cytokine profile (IFN-γ but not IL-4), the production of high IgG2a and low IgG1 titers, and a cytotoxic T-lymphocyte (CTL) response [19][20][21][22][23]. Horner et al [13] expanded on previous observations regarding the potent Th1-biased adjuvant effect of CpG-ODN to demonstrate that, in addition, it is as good a mucosal adjuvant as CT.…”

“…Gastric antibody was eluted from the wicks into a protease inhibitor cocktail containing 5% nonfat dry milk, 1 µg/ml aprotinin (Sigma, St Louis, MO), and 10 µmol / l leupeptin (Sigma). Samples were vortexed vigorously and insoluble material was removed by centrifugation [19].…”

Helicobacter pyloriflagella: antigenic profile and protective immunity

“…Numerous antigens have been examined as potential vaccine candidates, including whole-cell lysate preparations, and subunit vaccines incorporating urease, heat shock proteins, catalase and CagA (Chen et al, 1992;Ferrero et al, 1994Ferrero et al, , 1995Yamaoka et al, 1996;Radcliff et al, 1997). Live vaccine vectors such as adenovirus and Salmonella serovars encoding Helicobacter antigens have also been investigated (Jiang et al, 1999;Bumann et al, 2001). Although all have successfully produced a reduction in colonization in vaccine recipients, none have completely protected the host against infection.…”