Protection of immunosuppressed mice against translocation of Pseudomonas aeruginosa from the gut by oral immunization with recombinant Pseudomonas aeruginosa outer membrane protein I expressing Salmonella dublin

Toth, A.; Schödel, Florian; Duchêne, Michael; Massarrat, Kyros; Blum, B.; Schmitt, Anja; Domdey, Horst; Specht, Bernd-Ulrich von

doi:10.1016/0264-410x(94)90246-1

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…challenge of P. aeruginosa (25). Vaccination with a Salmonella enterica serovar Dublin strain expressing P. aeruginosa OprI was able to protect about 10 to 20% of Cy-treated vaccinated mice from oral challenge with P. aeruginosa (23). However, these mice received eight vaccinations or boosters to achieve this low level of protection, while our mice received only one vaccination.…”

Section: Discussionmentioning

confidence: 78%

Vaccination againstPseudomonas aeruginosaPneumonia in Immunocompromised Mice

Scarff

Goldberg

2008

Clin Vaccine Immunol

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Immunocompromised patients are highly susceptible to infection with Pseudomonas aeruginosa. Our laboratory previously showed that intranasal administration of an attenuated Salmonella strain expressing the P. aeruginosa lipopolysaccharide O antigen was effective in clearing bacteria and preventing mortality in wild-type mice after intranasal challenge. We were interested in investigating the efficacy of this vaccine strategy in immunocompromised mice. Mice rendered leukopenic or neutropenic by intraperitoneal treatment with cyclophosphamide (Cy) or RB6-8C5 antibody, respectively, were more susceptible to P. aeruginosa pneumonia than their nontreated counterparts, demonstrating 50% lethal doses several logs lower than that in wild-type mice. This hypersusceptiblity was also associated with bacterial dissemination to the liver and spleen and increased lung permeability in Cy mice. Vaccination of the mice prior to treatment resulted in better survival and lower bacterial loads compared to vector-immunized mice. Although the treatments had no effect on antibody titers, this level of protection was still lower than that seen in untreated vaccinated mice. Administration of antibodies directly to the site of infection at the time of bacterial delivery prolonged survival and lowered bacterial loads in the immunocompromised mice. These results demonstrate the importance of white blood cells while still suggesting a critical role for antibodies in protection against P. aeruginosa infection.Pseudomonas aeruginosa is an important opportunistic pathogen that is associated with infections in cystic fibrosis patients, burn patients, patients on ventilators, and contact lens wearers. Another important infection group consists of immunocompromised individuals, such as those undergoing chemotherapy or AIDS patients (11,14,17). Infections in these patient populations are difficult to treat, partly due to the innate antibiotic resistance of P. aeruginosa and partly due to the immunocompromised status of the patient. A particular problem associated with pneumonia in immunocompromised patients is bacteremia, which allows the bacteria to spread to other organs (11,14,17).Recently, host factors contributing to dissemination of P. aeruginosa were investigated with a gastrointestinal model of colonization leading to infection (12). Mice previously infected with P. aeruginosa in the intestinal tract and then rendered neutropenic had increased dissemination and mortality. Two methods of inducing of neutropenia were used in that study (12): treatment with cyclophosphamide (Cy) and treatment with the RB6-8C5 antibody specific for the Ly6 antigen on the surface of neutrophils (9). Neutropenic mice were also used by Vance et al. (24) as a model to monitor dissemination of type III secretion system (TTSS) mutants of P. aeruginosa.Previous work in our laboratory characterized a vaccine that confers serotype-specific protection against P. aeruginosa challenge (5). The vaccine consists of Salmonella enterica serovar Typhimurium strain SL3261, an ...

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Section: Discussionmentioning

confidence: 78%

Vaccination againstPseudomonas aeruginosaPneumonia in Immunocompromised Mice

Scarff

Goldberg

2008

Clin Vaccine Immunol

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“…Other P. aeruginosa vaccine strategies have focused on the outer membrane proteins (OMPs) OprF [101–105] and OprI [106–108], which are antigenically related among all serotypes [109], as well as OprF/I fusion proteins [102,110]. Initial studies of OMPs as vaccines were confounded by LPS contamination of OMP preparations but did show evidence of serotype-heterologous protection with a purified OprF vaccine in addition to the homologous protection elicited by contaminating LPS [111,112].…”

Section: Outer Membrane Proteinsmentioning

confidence: 99%

Vaccines forPseudomonas aeruginosa: a long and winding road

Priebe¹,

Goldberg²

2014

Expert Review of Vaccines

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106

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Summary Despite the recognition of Pseudomonas aeruginosa is an opportunistic pathogen, no vaccine against this bacteria have come to market. This review describes the current state-of-the-art in vaccinology for this bacterium. This includes a discussion of those at risk for infection, the types of vaccines and the approaches for empirical and targeted antigen selection under development, as well as a perspective on where the field should go. In addition, the challenges in developing a vaccine for those individuals at risk are discussed.

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“…OPRs, which induce cross-protective immunity among all 17 known P. aeruginosa serotypes (38), can be produced by recombinant DNA technology free of contaminating P. aeruginosa LPS. Additionally, cloned genes of OPRs would be applicable for naked DNA immunization (4,8) or could be transfected into special vectors such as nonpathogenic Salmonella strains to induce a mucosal immune response (34,50). The efficacy of OPRs as a vaccine candidate was shown by us and other research groups (12,13,18,19,35,52,53) in various animal models.…”

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confidence: 99%

Safety and Immunogenicity of a Pseudomonas aeruginosa Hybrid Outer Membrane Protein F-I Vaccine in Human Volunteers

Mansouri

Gabelsberger²,

Knapp

et al. 1999

Infect Immun

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A hybrid protein [Met-Ala-(His)6OprF190–342-OprI21–83] consisting of the mature outer membrane protein I (OprI) and amino acids 190 to 342 of OprF of Pseudomonas aeruginosa was expressed in Escherichia coli and purified by Ni2+ chelate-affinity chromatography. After safety and pyrogenicity evaluations in animals, four groups of eight adult human volunteers were vaccinated intramuscularly three times at 4-week intervals and revaccinated 6 months later with either 500, 100, 50, or 20 μg of OprF-OprI adsorbed onto A1(OH)3. All vaccinations were well tolerated. After the first vaccination, a significant rise of antibody titers against P. aeruginosaOprF and OprI was measured in volunteers receiving the 100- or the 500-μg dose. After the second vaccination, significant antibody titers were measured for all groups. Elevated antibody titers against OprF and OprI could still be measured 6 months after the third vaccination. The capacity of the elicited antibodies to promote complement binding and opsonization could be demonstrated by a C1q-binding assay and by the in vitro opsonophagocytic uptake ofP. aeruginosa bacteria. These data support the continued development of an OprF-OprI vaccine for use in humans.

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Protection of immunosuppressed mice against translocation of Pseudomonas aeruginosa from the gut by oral immunization with recombinant Pseudomonas aeruginosa outer membrane protein I expressing Salmonella dublin

Cited by 15 publications

References 25 publications

Vaccination againstPseudomonas aeruginosaPneumonia in Immunocompromised Mice

Vaccination againstPseudomonas aeruginosaPneumonia in Immunocompromised Mice

Vaccines forPseudomonas aeruginosa: a long and winding road

Safety and Immunogenicity of a Pseudomonas aeruginosa Hybrid Outer Membrane Protein F-I Vaccine in Human Volunteers

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