Attenuated
            <i>Salmonella enterica</i>
            Serovar Typhi Expressing Urease Effectively Immunizes Mice against
            <i>Helicobacter pylori</i>
            Challenge as Part of a Heterologous Mucosal Priming-Parenteral Boosting Vaccination Regimen

Londoño-Arcila, Patricia; Freeman, Donna J.; Kleanthous, Harry; O’Dowd, Aisling; Lewis, Susan J.; Turner, A. Keith; Rees, Emma L.; Tibbitts, Timothy; Greenwood, Judith; Monath, Thomas P.; Darsley, Michael J.

doi:10.1128/iai.70.9.5096-5106.2002

Cited by 73 publications

(42 citation statements)

References 60 publications

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“…In particular, primeboost vaccination protocols, combining mucosal and parenteral administration, seem to be more promising than mucosal or parenteral alone in eliciting both cellular and humoral response (18,37), as well as in providing protection against H. pylori challenge (18). Although these protection data have been obtained by prophylactic vaccination, they should be taken in account in attempts to design a more efficacious protocol of therapeutic vaccination since, in this case, the infection can act as an effective mucosal priming (35).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

et al. 2004

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Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa causing gastritis and peptic ulcer and increasing the risk of gastric cancer. The efficacy of current antibiotic-based therapies can be limited by problems of patient compliance and increasing antibiotic resistance; the vaccine approach can overcome these limits. The present study describes the therapeutic vaccination of experimentally H. pyloriinfected beagle dogs, an animal model that reproduces several aspects of the human infection with H. pylori. The vaccine consisted of three recombinant H. pylori antigens, CagA, VacA, and NAP, formulated at different doses (10, 25, or 50 g each) with alum and administered intramuscularly either weekly or monthly. No adverse effects were observed after vaccination and a good immunoglobulin G response was generated against each of the three antigens. Bacterial colonization and gastritis were decreased after the completion of the vaccination cycle, especially in the case of the monthly immunization schedule. In conclusion, therapeutic vaccination in the beagle dog model was safe and immunogenic and was able to limit H. pylori colonization and the related gastric pathology.Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of Ͼ50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13,38).Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30).To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2,17,26,34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28,29).Most of the examples of vaccination against H. pylori in animal models reported in the...

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Section: Discussionmentioning

confidence: 99%

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

et al. 2004

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“…AF233683). X47 had been used primarily for studies of immune responses and for vaccine development (Ermak et al, 1998;Kleanthous et al, 2001;Londono-Arcila et al, 2002), but is becoming increasingly popular for mutational analyses (Jeong et al, 2001;O'Rourke et al, 2003), in part because it is easier than SS1 to transform with mutated DNAs. Strain X47 lacks the cag pathogenicity island entirely, but contains an s1 allele of vacA (GenBank accession no.…”

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori tissue tropism: mouse-colonizing strains can target different gastric niches

et al. 2003

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Studies with the mouse-adapted Helicobacter pylori strain SS1 had supported an idea that infections by this pathogen start in the gastric antrum and spread to the corpus after extensive mucosal damage. This paper shows that the unrelated strain X47 colonizes the corpus preferentially. Differences between strains in preferred gastric region were detected by co-inoculating mice with a mixture of SS1 and X47, and genotyping H. pylori recovered after 2-8 weeks of infection by vacA s allele PCR and RAPD fingerprinting. Mixed infections were found in each of 59 co-inoculated young C57BL/6J mice. On average, however, SS1 was fourfold more abundant than X47 in the antrum and X47 was threefold more abundant than SS1 in the corpus. Similar results were obtained in mice inoculated first with one strain and then the other strain 2 weeks later. SS1 was even more abundant in the antrum of elderly (>1 year old) mice (97 % of isolates). Qualitatively similar SS1 and X47 tissue distributions were seen using unrelated mouse lines (AKR/J, A/J, DBA/2J, BALB/cJ, LG/J, SM/J), but with significantly different SS1 : X47 ratios in some cases. These results suggest the existence of at least two distinct gastric niches whose characteristics may be affected by host genotype and age (physiology), and indicate that strains differ in how effectively they colonize each niche. Differences among gastric regions and the mixed infections that these allow may contribute to H. pylori diversity and genome evolution.

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“…En modalidad terapéutica sólo se observa reducción de la carga en ratones C57BL/ 6 24 . Por otro lado, Londoño y cols 25 obtuvieron resultados similares en protección y aumento de la respuesta humoral y celular, caracterizada esta última por un aumento inespecífico en la secreción de citoquinas, al utilizar S. enterica serovar Typhi con un sistema de expresión para UreAB inducible, en modalidad profiláctica. Dicha protección y aumento en la respuesta inmune estaría asociada a la inmunización primaria más la presencia de un booster luego de varias semanas 25 .…”

Section: Factibilidad De Una Vacuna: Modelos Animalesunclassified

“…Por otro lado, Londoño y cols 25 obtuvieron resultados similares en protección y aumento de la respuesta humoral y celular, caracterizada esta última por un aumento inespecífico en la secreción de citoquinas, al utilizar S. enterica serovar Typhi con un sistema de expresión para UreAB inducible, en modalidad profiláctica. Dicha protección y aumento en la respuesta inmune estaría asociada a la inmunización primaria más la presencia de un booster luego de varias semanas 25 . La administración de vacunas de ADN utilizando antígenos como ureasa, catalasa y proteínas de shock térmico (heat shock protein-hsp) A y B, mostraron también reducción significativa de la carga bacteriana en administraciones intracutáneas e intranasales de los plásmidos vacuna 26,27 .…”

Section: Factibilidad De Una Vacuna: Modelos Animalesunclassified

Vacunas en desarrollo: Helicobacter pylori

2006

Rev. chil. infectol.

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Vaccines under development: Helicobacter pyloriHelicobacter pylori causes gastrointestinal disease including peptic ulcer and gastric cancer. An H. pylori vaccine is relevant because of the high prevalence of the infection and its associated complications. Extensive use of traditional antimicrobial therapies to eradicate H. pylori is not feasable, specially in developing countries, in part because of their high cost, associated adverse effects, the risk of reinfection, and the emergence of antimicrobial drug resistance. Numerous animal studies have been performed to determine infection outcomes and to explore the feasibility of a vaccine eradication or prevention of infection. These animal models with the possible exception of monkeys, have not been sufficient to address fundamental issues due to controversial results. A human model of H. pylori infection needs to be developed aimed to select an optimum vaccine candidate. The ultimate scientific goal will be to develop field studies using advanced vaccine candidates, but the current state of knowledge does is insufficient and has provided such candidates. These studies need to be designed in order to provide relevant information on immunity and pathogenesis associated to H. pylori.

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Attenuated Salmonella enterica Serovar Typhi Expressing Urease Effectively Immunizes Mice against Helicobacter pylori Challenge as Part of a Heterologous Mucosal Priming-Parenteral Boosting Vaccination Regimen

Abstract: Recombinant vaccine strains of

Cited by 73 publications

References 60 publications

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

Therapeutic Vaccination againstHelicobacter pyloriin the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

Helicobacter pylori tissue tropism: mouse-colonizing strains can target different gastric niches

Vacunas en desarrollo: Helicobacter pylori

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