Enhanced Immunogenicity in the Murine Airway Mucosa with an Attenuated<i>Salmonella</i>Live Vaccine Expressing OprF-OprI from<i>Pseudomonas aeruginosa</i>

Arnold, H. Greenberg; Bumann, Dirk; Felies, Melanie; Gewecke, Britta; Sörensen, Meike; Gessner, J. Engelbert; Freihorst, Joachim; Specht, B U von; Baumann, Ulrich

doi:10.1128/iai.72.11.6546-6553.2004

Cited by 29 publications

(11 citation statements)

References 39 publications

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“…The experiment showed a tendency but did not yield significant effects of MALP-2 as a mucosal adjuvant in this setting. It is conceivable that using the intranasal route [14] or better immunogenic outer membrane proteins of P. aeruginosa might produce a better effect [1].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of TLR-2/6 Ligation in Pulmonary Bacterial Infection and Immunization with Pseudomonas aeruginosa

et al. 2009

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Pseudomonas aeruginosa (P. aeruginosa) is the major pathogen in nosocomial and life-threatening infections of immunocompromised or critically ill patients. The macrophage-activating lipopeptide-2 (MALP-2) activates the immune system via Toll-like receptors (TLR) 2 and 6 and leads to an accumulation of immune cells in lungs of young adult (8-10 week old) rats after intratracheal application. This is characterized by a high increase of granulocyte numbers in the BAL 24 h after MALP-2 treatment. It was hypothesized that MALP-2 may have a positive effect on the clinical course of an experimental infection. Therefore, rats were treated with MALP-2 at different time points following an infection with P. aeruginosa. The effect of MALP-2 in combination with immunization with inactivated P. aeruginosa was also investigated. Rats (n = 10) were infected intratracheally (i.t.) with 1 x 10(8) CFU P. aeruginosa on day 0. They were treated on day -3, -1, 0 and +1 with 2.5 microg MALP-2 or the vehicle i.t. In additional experiments, rats were immunized on day -21 and -14 with 1 x 10(8) CFU of inactivated P. aeruginosa bacteria and 2.5 microg MALP-2 or vehicle with 1 x 10(8) CFU of inactivated bacteria and isopropanol. The clinical score, rectal temperature and weight of the rats were checked in both treatment and immunization experiments twice a day. On day 2 they were sacrificed, CFU were determined in the left lung, the right lung being used for histology. In the group treated with MALP-2 1 day prior to infection significant effects were seen: The rectal temperature was about 2 degrees C higher in comparison to the controls at 6 h and also 1 day after infection. Both the symptoms of the infection and the weight loss were significantly reduced. In addition, the CFU and the inflammation in the lung tissue were significantly lower. These effects were not observed after treatment on day -3, 0 or +1. The MALP-2 enhanced immunization only resulted in a tendency to clinical improvement. In conclusion, local immunostimulation at the appropriate time can enhance the host defense against bacteria in the lung.

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Section: Discussionmentioning

confidence: 99%

Beneficial Effects of TLR-2/6 Ligation in Pulmonary Bacterial Infection and Immunization with Pseudomonas aeruginosa

et al. 2009

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“…Protection against respiratory pathogens induced by oral vaccination also has been documented in mice [15]–[17], and evidence exists that bacillus Calmette-Guerin (BCG) administered orally is protective against tuberculosis in people and animals [18]–[20]. Moreover, inactivated bacteria and viruses also can elicit protective immune responses against systemic infections, including those of the respiratory tract [21]–[24].…”

Section: Introductionmentioning

confidence: 99%

Effects of Administration of Live or Inactivated Virulent Rhodococccus equi and Age on the Fecal Microbiome of Neonatal Foals

et al. 2013

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Background Rhodococcus equi is an important pathogen of foals. Enteral administration of live, virulent R. equi during early life has been documented to protect against subsequent intrabronchial challenge with R. equi, indicating that enteral mucosal immunization may be protective. Evidence exists that mucosal immune responses develop against both live and inactivated micro-organisms. The extent to which live or inactivated R. equi might alter the intestinal microbiome of foals is unknown. This is an important question because the intestinal microbiome of neonates of other species is known to change over time and to influence host development. To our knowledge, changes in the intestinal microbiome of foals during early life have not been reported. Thus, the purpose of this study was to determine whether age (during the first month of life) or administration of either live virulent R. equi (at a dose reported to protect foals against subsequent intrabronchial challenge, viz., 1×1010 colony forming units [CFU]) or inactivated virulent R. equi (at higher doses, viz., 2×1010 and 1×1011 [CFU]) altered the fecal microbiome of foals.Methodology/Principal FindingsFecal swab samples from 42 healthy foals after vaccination with low-dose inactivated R. equi (n = 9), high-dose inactivated R. equi (n = 10), live R. equi (n = 6), control with cholera toxin B (CTB, n = 9), and control without CTB (n = 8) were evaluated by 454-pyrosequencing of the 16S rRNA gene and by qPCR. No impact of treatment was observed among vaccinated foals; however, marked and significant differences in microbial communities and diversity were observed between foals at 30 days of age relative to 2 days of age.ConclusionsThe results suggest age-related changes in the fecal microbial population of healthy foals do occur, however, mucosal vaccination does not result in major changes of the fecal microbiome in foals.

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“…Because P. aeruginosa colonizes the respiratory tract, high titers of local IgA and IgG in the airways are desirable . Oral administration with Salmonella vaccines induces strong mucosal responses with IgA and IgG antibodies in gut‐associated lymphoid tissue . However, oral vaccination does not induce enhanced immune responses in the respiratory mucosa or only induces limited immune responses in the upper airways .…”

Section: Discussionmentioning

confidence: 99%

Salmonella Typhimurium strain expressing OprF‐OprI protects mice against fatal infection by Pseudomonas aeruginosa

Zhang¹,

Sun²,

Gu³

et al. 2015

Microbiology and Immunology

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Pseudomonas aeruginosa poses a major threat to human health and to the mink industry. Thus, development of vaccines that elicit robust humoral and cellular immunity against P. aeruginosa is greatly needed. In this study, a recombinant attenuated Salmonella vaccine (RASV) that expresses the outer membrane proteins fusion OprF 190-342 -OprI 21-83 (F1I2) from P. aeruginosa was constructed and the potency of this vaccine candidate assessed by measuring F1I2-specific humoral immune responses upon vaccination through s.c. or oral routes. S.C. administration achieved higher serum IgG titers and IgA titers in the intestine and induced stronger F1I2-specific IgG and IgA titers in lung homogenate than did oral administration, which resulted in low IgG titers and no local IgA production. High titers of IFN-g, IL-4, and T-lymphocyte subsets induced a mixed Th1/Th2 response in mice immunized s.c., indicating elicitation of cellular immunity. Importantly, when immunized mice were challenged with P. aeruginosa by the intranasal route 30 days after the initial immunization, s.c. vaccination achieved 77.78% protection, in contrast to 41.18% via oral administration and 66.67% via Escherichia coli-expressed F1I2 (His-F1I2) vaccination. These results indicate that s.c. vaccination provides a better protective response against P. aeruginosa infection than do oral administration and the His-F1I2 vaccine.Key words outer membrane protein, Pseudomonas aeruginosa, Salmonella Typhimurium, subcutaneous vaccination.Pseudomonas aeruginosa is a major cause of pulmonary infection, causing cystic fibrosis-and non-cystic fibrosisrelated bronchiectasis and chronic obstructive pulmonary disease. It is also a common pathogen responsible for hospital-acquired infections in burn, transplant, cancer and intensive care unit patients (1). Various animals, including dogs, dairy cows, horses, mink and foxes, are believed to be susceptible to P. aeruginosa (2). In particular, P. aeruginosa has been a major cause of hemorrhagic pneumonia in mink for the last 50 years, resulting in serious losses in the Chinese mink industry (2, 3). Although there have been considerable advances in antimicrobial therapy for the treatment and control of P. aeruginosa infection, undesirable adverse effects remain a persistent problem, primarily because of the natural resistance of this pathogen and its formidable ability to acquire resistance to multiple antimicrobial agents by various mechanisms. Therefore, measures to effectively contain P. aeruginosa infection are urgently needed. List of Abbreviations: APC, antigen-presenting cell; DAP, 2,6-diaminopimelic acid; DTH, delayed-type hypersensitivity; F1, part of outer membrane proteins F ) of Pseudomonas aeruginosa; I2, part of outer membrane proteins I (OprI 21-83 ) of Pseudomonas aeruginosa; PQ, Salmonella Typhimurium LH430 with asd deleted; RASV, recombinant attenuated Salmonella vaccine.

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Enhanced Immunogenicity in the Murine Airway Mucosa with an AttenuatedSalmonellaLive Vaccine Expressing OprF-OprI fromPseudomonas aeruginosa

Cited by 29 publications

References 39 publications

Beneficial Effects of TLR-2/6 Ligation in Pulmonary Bacterial Infection and Immunization with Pseudomonas aeruginosa

Beneficial Effects of TLR-2/6 Ligation in Pulmonary Bacterial Infection and Immunization with Pseudomonas aeruginosa

Effects of Administration of Live or Inactivated Virulent Rhodococccus equi and Age on the Fecal Microbiome of Neonatal Foals

Salmonella Typhimurium strain expressing OprF‐OprI protects mice against fatal infection by Pseudomonas aeruginosa

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