155 results on '"Pseudomonas Vaccines"'
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2. Structural and biological insights into outer membrane protein lipotoxin F of Pseudomonas aeruginosa: Implications for vaccine application.
- Author
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Cheng X, Chen Z, Gao C, Zhang Y, Yang L, Wan J, Wei Y, Zeng S, Zhang Y, Zhang Y, Li Y, Zhang W, Zou Q, Lu G, and Gu J
- Subjects
- Humans, Vaccination, Pseudomonas Vaccines, Antibodies, Bacterial, Bacterial Proteins, Pseudomonas aeruginosa
- Abstract
Due to the increasing antibiotic resistance of Pseudomonas aeruginosa (PA), an effective vaccine is urgently needed. However, no PA vaccine has been approved to date, and new protective antigens are needed to improve their efficacy. In this study, Luminex beads were used to identify new candidate antigens, after which their crystal structure was determined, and their potential contribution to bacterial pathogenesis was assessed in vitro and in vivo. Notably, a significant antibody response against the outer membrane protein LptF (lipotoxin F) was detected in sera from 409 volunteers. Moreover, vaccination with recombinant LptF conferred effective protection in an acute PA pneumonia model. The crystal structure showed that LptF comprises a 3-stranded β-sheet (β1-β3) and three α-helices (α1-α3) that are organized in an α/β/α/β/α/β pattern, which is structurally homologous to OmpA and related outer membrane proteins. In addition, LptF binds to peptidoglycan in an atypical manner, contributing to the pathogenesis and survival of PA under stress. Our data indicate that LptF is an important virulence factor and thus a promising candidate antigen for PA vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
- Full Text
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3. Multicomponent Pseudomonas aeruginosa vaccines eliciting Th17 cells and functional antibody responses confer enhanced protection against experimental acute pneumonia in mice
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Mohammad Omar Faruk Shaikh, Matthew M. Schaefers, Christina Merakou, Marco DiBlasi, Sarah Bonney, Tiffany Liao, David Zurakowski, Margaret Kehl, David E. Tabor, Antonio DiGiandomenico, and Gregory P. Priebe
- Subjects
Pseudomonas Vaccines ,Immune Sera ,Immunology ,Pneumonia ,Antibodies, Bacterial ,Microbiology ,Mice ,Infectious Diseases ,Bacterial Proteins ,Immunoglobulin G ,Pseudomonas aeruginosa ,Antibody Formation ,Type III Secretion Systems ,Animals ,Th17 Cells ,Pseudomonas Infections ,Parasitology - Abstract
The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. aeruginosa type III secretion system protein, PopB elicits a strong Th17 response in mice after intranasal (IN) immunization and confers antibody-independent protection against pneumonia in mice. In the current study, we evaluated the immunogenicity and protective efficacy in mice of the combination of PopB (purified with its chaperone protein PcrH) and OprF/I, an outer membrane hybrid fusion protein, compared to immunization with the proteins individually either by the intranasal (IN) or subcutaneous (SC) routes. Our results show that after vaccination, a Th17 recall response from splenocytes was detected only in mice vaccinated with PopB/PcrH, either alone or in combination with OprF/I. Mice that were immunized with the combination of PopB/PcrH and OprF/I had enhanced protection in an acute lethal P. aeruginosa pneumonia model, regardless of vaccine route, compared to the mice vaccinated the with either alone or adjuvant control. Immunization generated IgG titers against the vaccine proteins and whole P. aeruginosa cells. Interestingly, none of these antisera had opsonophagocytic killing activity, but antisera from mice immunized with vaccines containing OprF/I had the ability to block IFN-γ binding to OprF/I, a known virulence mechanism. Hence, vaccines combining PopB/PcrH with OprF/I that elicit functional antibodies lead to a broadly and potently protective vaccine against P. aeruginosa pulmonary infections.
- Published
- 2022
4. Intranasal Delivery of Antigen-Coated Polymer Particles Protects against
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Zennia Jean C, Gonzaga, Jinyong, Zhang, and Bernd H A, Rehm
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Epitopes ,Mice ,Pseudomonas Vaccines ,Polymers ,Pseudomonas aeruginosa ,Animals ,Aluminum Hydroxide ,Pseudomonas Infections ,Antibodies, Bacterial - Published
- 2022
5. Protective Potential of Conjugated P. aeruginosa LPS –PLGA Nanoparticles in Mice as a Nanovaccine
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Leila, Safari Zanjani, Reza, Shapoury, Mehrouz, Dezfulian, Mehdi, Mahdavi, and Mehdi, Shafieeardestani
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Lipopolysaccharides ,Antigens, Bacterial ,Mice, Inbred BALB C ,Pseudomonas Vaccines ,lps ,technology, industry, and agriculture ,macromolecular substances ,pseudomonas aeruginosa ,Mice ,Polylactic Acid-Polyglycolic Acid Copolymer ,lcsh:Biology (General) ,Animals ,Nanoparticles ,nanovaccine ,lipids (amino acids, peptides, and proteins) ,plga ,lcsh:QH301-705.5 - Abstract
Background: Pseudomonas aeruginosa has an important role in nosocomial infections. Objective: To evaluate biological activity of the detoxified LPS (D-LPS) entrapped into Poly lactic-co-glycolic acid (PLGA) nanoparticles. Materials: LPS was extracted and detoxified from the P. aeruginosa strain PAO1. The D-LPS, conjugated to the PLGA nanoparticles with 1-ethyl-3-dimethyl aminopropyl carbodiimide (EDAC) and N-hydroxy-succinimide (NHS). The connection was evaluated by FTIR (Fourier transform infrared), Zetasizer, and Atomic Force Microscope (AFM). The BALB/c mice injected intramuscularly with the D-LPS-PLGA with two-week intervals and then challenged two weeks after the last immunization. The bioactivity of the induced specific antisera and cytokines responses against D-LPS-PLGA antigen was assessed by ELISA. Results: D-LPS-PLGA conjugation was confirmed by FTIR, Zetasizer, and AFM. The ELISA results showed that D-LPS was successful in the stimulation of the humoral immune response. The immune responses raised against the D-LPS-PLGA, significantly decreased bacterial titer in the spleen of the immunized mice after challenge with PAO1 strain in comparison with the control groups. Conclusion: The conjugation of the bacterial LPS to the PLGA nanoparticle increased their functional activity by decrease in bacterial dissemination and increase the killing of opsonized bacteria.
- Published
- 2020
6. A novel inactivated whole-cell Pseudomonas aeruginosa vaccine that acts through the cGAS-STING pathway
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Xueyuan Liao, Cui-Cui Ma, Hailong Pan, Li Zhang, Wenfang Li, Mao Lian, Xingjun Cheng, Xiao Ma, Zhixue Shen, Boguang Jiang, Yingjie Luo, and Zhenling Wang
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endocrine system ,Cancer Research ,Pseudomonas Vaccines ,QH301-705.5 ,medicine.disease_cause ,Article ,Mice ,In vivo ,Genetics ,medicine ,Animals ,Pseudomonas Infections ,Biology (General) ,Mice, Knockout ,CD86 ,Vaccines ,Pseudomonas aeruginosa ,business.industry ,Pyroptosis ,Membrane Proteins ,Nucleotidyltransferases ,In vitro ,Vaccination ,RAW 264.7 Cells ,Immunology ,Medicine ,Infection ,business ,CD80 ,CD8 ,Signal Transduction - Abstract
Pseudomonas aeruginosa infection continues to be a major threat to global public health, and new safe and efficacious vaccines are needed for prevention of infections caused by P. aeruginosa. X-ray irradiation has been used to prepare whole-cell inactivated vaccines against P. aeruginosa infection. However, the immunological mechanisms of X-ray-inactivated vaccines are still unclear and require further investigation. Our previous study found that an X-ray-inactivated whole-cell vaccine could provide protection against P. aeruginosa by boosting T cells. The aim of the present study was to further explore the immunological mechanisms of the vaccine. Herein, P. aeruginosa PAO1, a widely used laboratory strain, was utilized to prepare the vaccine, and we found nucleic acids and 8-hydroxyguanosine in the supernatant of X-ray-inactivated PAO1 (XPa). By detecting CD86, CD80, and MHCII expression, we found that XPa fostered dentritic cell (DC) maturation by detecting. XPa stimulated the cGAS-STING pathway as well as Toll-like receptors in DCs in vitro, and DC finally underwent apoptosis and pyroptosis after XPa stimulation. In addition, DC stimulated by XPa induced CD8+ T-cell proliferation in vitro and generated immunologic memory in vivo. Moreover, XPa vaccination induced both Th1 and Th2 cytokine responses in mice and reduced the level of inflammatory factors during infection. XPa protected mice in pneumonia models from infection with PAO1 or multidrug-resistant clinical isolate W9. Chronic obstructive pulmonary disease (COPD) mice immunized with XPa could resist PAO1 infection. Therefore, a new mechanism of an X-ray-inactivated whole-cell vaccine against P. aeruginosa infection was discovered in this study.
- Published
- 2021
7. Outbreak of Pseudomonas aeruginosa mastitis in a dairy cow herd in northern Greece and its control with an autogenous vaccine
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E J, Petridou, I A, Fragkou, S Q, Lafi, and N D, Giadinis
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Pseudomonas Vaccines ,Pseudomonas aeruginosa ,Animals ,Cattle ,Female ,Pseudomonas Infections ,Mastitis, Bovine ,Disease Outbreaks - Abstract
In a dairy cow herd consisted of herd of 200 lactating Holstein-Friesian cows and heifers, clinical signs of mastitis in 40 out of 170 animals were observed. Treatments with antibiotics were proved ineffective. Milk bacterial cultures from 15 affected animals revealed Pseudomonas aeruginosa. An autogenous vaccine was administered subcutaneously, twice in a month period, to all adults. Cases of clinical mastitis declined significantly (p⟨0.0001) during next 3 months.
- Published
- 2021
8. Assessment of the impact of manufacturing changes on the physicochemical properties of the recombinant vaccine carrier ExoProtein A
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Motoshi Suzuki, Raul Herrera, Nicholas J. MacDonald, Vu Nguyen, David L. Narum, L. Renee Olano, Patrick E. Duffy, Martin Burkhardt, Richard L. Shimp, and Karine Reiter
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Chemical Phenomena ,Pseudomonas Vaccines ,Virulence Factors ,Bacterial Toxins ,030231 tropical medicine ,Exotoxins ,Article ,law.invention ,Epitopes ,Mice ,03 medical and health sciences ,Immunogenicity, Vaccine ,0302 clinical medicine ,law ,Conjugate vaccine ,medicine ,Animals ,Humans ,Pseudomonas Infections ,Amino Acid Sequence ,030212 general & internal medicine ,Quality characteristics ,Total protein ,ADP Ribose Transferases ,Vaccines, Synthetic ,Chromatography ,General Veterinary ,General Immunology and Microbiology ,medicine.diagnostic_test ,Chemistry ,Spectrum Analysis ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Pseudomonas aeruginosa exotoxin A ,Recombinant Proteins ,Infectious Diseases ,Mixed-mode chromatography ,Immunoassay ,Recombinant DNA ,Molecular Medicine ,Peptides ,Protein Processing, Post-Translational - Abstract
Efforts to develop a vaccine for the elimination of malaria include the use of carrier proteins to assemble monomeric antigens into nanoparticles to maximize immunogenicity. Recombinant ExoProtein A (EPA) is a detoxified form of Pseudomonas aeruginosa Exotoxin A which has been used as a carrier in the conjugate vaccine field. A pilot-scale process developed for purification of EPA yielded product that consistently approached a preset upper limit for host cell protein (HCP) content per human dose. To minimize the risk of bulk material exceeding the specification, the purification process was redeveloped using mixed-mode chromatography resins. Purified EPA derived from the primary and redeveloped processes were comparable following full biochemical and biophysical characterization. However, using a process specific immunoassay, the HCP content was shown to decrease from a range of 0.14–0.24% w/w of total protein to below the level of detection with the revised process. The improved process reproducibly yields EPA with highly similar quality characteristics as the original process but with an improved profile for the HCP content.
- Published
- 2019
9. Lectin activity of Pseudomonas aeruginosa vaccine candidates PSE17-1, PSE41-5 and PSE54
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Michael P. Jennings, Kate L. Seib, Joe Tiralongo, Lauren E. Hartley-Tassell, Silvana Savino, Vega Masignani, Christopher J. Day, and Nicolai V. Bovin
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0301 basic medicine ,Glycan ,Pseudomonas Vaccines ,Virulence Factors ,Biophysics ,medicine.disease_cause ,Biochemistry ,Bacterial Adhesion ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bacterial Proteins ,Antigen ,Polysaccharides ,Lectins ,ABO blood group system ,medicine ,Humans ,Pseudomonas Infections ,Molecular Biology ,biology ,Pseudomonas aeruginosa ,Glycobiology ,Chemistry ,Pseudomonas ,Cell Biology ,Sialyl-Lewis A ,biology.organism_classification ,030104 developmental biology ,030220 oncology & carcinogenesis ,Pilin ,biology.protein - Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections most commonly in immunocompromised, cystic fibrosis (CF) and burns patients. The pilin and Pseudomonas lectins 1 (PA-IL) and 2 (PA-IIL) are known glycan-binding proteins of P. aeruginosa that are involved in adherence to host cells, particularly CF host airways. Recently, new P. aeruginosa surface proteins were identified by reverse vaccinology and tested in vivo as potential vaccine antigens. Three of these, namely PSE17-1, PSE41-5 and PSE54, were screened for glycan binding using glycan arrays displaying glycan structures representative of those found on human cells. Surface plasmon resonance was used to confirm the lectin activity of these proteins, and determined affinities with several host glycans to be in the nanomolar range. PSE17-1 binds hyaluronic acid and sialyl Lewis A and X. PSE41-5 binds terminal β-linked galactose structures, Lewis and ABO blood group antigens. PSE54 binds to ABO blood group antigens and some terminal β-linked galactose. All three proteins are novel lectins of P. aeruginosa with potential roles in infection of host cells.
- Published
- 2019
10. Intradermal vaccination with a Pseudomonas aeruginosa vaccine adjuvanted with a mutant bacterial ADP-ribosylating enterotoxin protects against acute pneumonia
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Derek Pociask, Sarah M. Baker, James B. McLachlan, John D. Clements, and Lisa A. Morici
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CD4-Positive T-Lymphocytes ,medicine.medical_treatment ,medicine.disease_cause ,Enterotoxins ,Mice ,0302 clinical medicine ,030212 general & internal medicine ,Lung ,biology ,Escherichia coli Proteins ,Interleukin-17 ,Vaccination ,Antibodies, Bacterial ,Infectious Diseases ,Acute Disease ,Pseudomonas aeruginosa ,Molecular Medicine ,Female ,Antibody ,Adjuvant ,Bacterial Outer Membrane Proteins ,Injections, Intradermal ,Pseudomonas Vaccines ,Bacterial Toxins ,030231 tropical medicine ,chemical and pharmacologic phenomena ,Microbiology ,Interferon-gamma ,03 medical and health sciences ,Immune system ,Adjuvants, Immunologic ,Immunity ,Pneumonia, Bacterial ,medicine ,Animals ,Pseudomonas Infections ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public Health, Environmental and Occupational Health ,medicine.disease ,Antibodies, Neutralizing ,Mice, Inbred C57BL ,Disease Models, Animal ,Pneumonia ,Immunization ,Immunoglobulin G ,Mutation ,biology.protein ,bacteria ,business ,Immunologic Memory - Abstract
Respiratory infections are a leading cause of morbidity and mortality globally. This is partially due to a lack of effective vaccines and a clear understanding of how vaccination route and formulation influence protective immunity in mucosal tissues such as the lung. Pseudomonas aeruginosa is an opportunistic pathogen capable of causing acute pulmonary infections and is a leading cause of hospital-acquired and ventilator-associated pneumonia. With multidrug-resistant P. aeruginosa infections on the rise, the need for a vaccine against this pathogen is critical. Growing evidence suggests that a successful P. aeruginosa vaccine may require mucosal antibody and Th1- and Th17-type CD4+ T cells to prevent pulmonary infection. Intradermal immunization with adjuvants, such as the bacterial ADP-Ribosylating Enterotoxin Adjuvant (BARE) double mutant of E. coli heat-labile toxin (dmLT), can direct protective immune responses to mucosal tissues, including the lungs. We reasoned that intradermal immunization with P. aeruginosa outer membrane proteins (OMPs) adjuvanted with dmLT could drive neutralizing antibodies and migration of CD4+ T cells to the lungs and protect against P. aeruginosa pneumonia in a murine model. Here we show that mice immunized with OMPs and dmLT had significantly more antigen-specific IgG and Th1- and Th17-type CD4+ memory T cells in the pulmonary environment compared to control groups of mice. Furthermore, OMPs and dmLT immunized mice were significantly protected against an otherwise lethal lung infection. Protection was associated with early IFN-γ and IL-17 production in the lungs of immunized mice. These results indicate that intradermal immunization with dmLT can drive protective immunity to the lung mucosa and may be a viable vaccination strategy for a multitude of respiratory pathogens.
- Published
- 2019
11. Aluminum (oxy) Hydroxide Nanorods Activate an Early Immune Response in Pseudomonas aeruginosa Vaccine
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Yali Hou, Houxiang Hu, Yingli Chen, Fenglin Lv, Yang Feng, Jun Yang, and Leilei He
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0301 basic medicine ,Materials science ,Pseudomonas Vaccines ,medicine.medical_treatment ,Aluminum Hydroxide ,02 engineering and technology ,Immunoglobulin G ,Cell Line ,Microbiology ,Mice ,03 medical and health sciences ,Immune system ,Adjuvants, Immunologic ,Antigen ,Aluminum Oxide ,medicine ,Animals ,General Materials Science ,Antigens, Bacterial ,Nanotubes ,biology ,Vaccination ,021001 nanoscience & nanotechnology ,Antibodies, Bacterial ,Immunity, Humoral ,Bacterial vaccine ,030104 developmental biology ,Pseudomonas aeruginosa ,biology.protein ,Female ,Bacterial antigen ,0210 nano-technology ,Adjuvant - Abstract
Bacterial vaccines have been widely used to prevent infectious diseases, especially in veterinary medicine. Although there are many reports on bacterin adjuvants, only a few contain innovations in bacterin adjuvants. Taking this into consideration, in this study we designed and synthesized a new aluminum (oxy) hydroxide (AlOOH) nanorod (Al-NR) with a diameter of 200 ± 80 nm and a length of 1.1 ± 0.6 μm. Using whole- Pseudomonas aeruginosa PAO1 as antigens, we showed that the bacterial antigens of P. aeruginosa PAO1 adsorbed on the Al-NRs induced a quick and stronger antigen-specific antibody response than those of the other control groups, especially in the early stage of immunization. Furthermore, the level of antigen-specific IgG was approximately 4-fold higher than that of the no adjuvant group and 2.5-fold higher than those of other adjuvant groups in the first week after the initial immunization. The potent adjuvant activity of the Al-NRs was attributed to the rapid presentation of antigen adsorbed on them by APCs. Additionally, Al-NRs induced a milder local inflammation than the other adjuvants. In short, we confirmed that Al-NRs, enhancing both humoral and cellular immune responses, are a potentially promising vaccine adjuvant delivery system for inhibiting the whole- Pseudomonas aeruginosa infection.
- Published
- 2018
12. PLGA-encapsulation of the Pseudomonas aeruginosa PopB vaccine antigen improves Th17 responses and confers protection against experimental acute pneumonia
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Gally Reznor, Roger Lu, Matthew M. Schaefers, Boaz Mizrahi, Gregory P. Priebe, Biyan Duan, and Daniel S. Kohane
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0301 basic medicine ,Pseudomonas Vaccines ,medicine.medical_treatment ,Enzyme-Linked Immunosorbent Assay ,Spleen ,macromolecular substances ,medicine.disease_cause ,Article ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bacterial Proteins ,Polylactic Acid-Polyglycolic Acid Copolymer ,Pneumonia, Bacterial ,medicine ,Splenocyte ,Animals ,Pseudomonas Infections ,Lung ,Administration, Intranasal ,Antigens, Bacterial ,Drug Carriers ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,Pseudomonas aeruginosa ,Interleukin-17 ,Lethal dose ,technology, industry, and agriculture ,Public Health, Environmental and Occupational Health ,Flow Cytometry ,Survival Analysis ,Bacterial Load ,Disease Models, Animal ,PLGA ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Vaccines, Subunit ,Th17 Cells ,Molecular Medicine ,Female ,Nasal administration ,Interleukin 17 ,Adjuvant ,030215 immunology - Abstract
The Pseudomonas aeruginosa type III secretion system protein PopB and its chaperon protein PcrH, when co-administered with the adjuvant curdlan, elicit Th17 responses after intranasal immunization of mice. These PopB/PcrH-curdlan vaccines protect mice against acute lethal pneumonia in an IL-17-dependent fashion involving CD4 helper T cells secreting IL-17 (Th17 cells). In this study, we tested whether encapsulation of PopB/PcrH in poly-lactic-co-glycolic acid (PLGA) nanoparticles could elicit Th17 responses to PopB. Recombinant PopB/PcrH or PcrH alone was encapsulated into PLGA nanoparticles. Mice (FVB/N) were intranasally immunized with the PLGA-PopB/PcrH nanoparticles, PLGA-PcrH nanoparticles, PLGA alone, or PopB/PcrH alone. The protective efficacy was assessed in an acute lung infection model with a lethal dose of an ExoU-producing version of P. aeruginosa strain PAO1. Th17 responses were assayed by intracellular flow cytometry and by ELISA for IL-17 in supernatants of splenocytes co-cultured with purified PopB/PcrH. PLGA-PopB/PcrH-immunized mice showed 3-4-fold higher Th17 responses both in the lung and in the spleen compared to mice immunized with empty PLGA or PopB/PcrH alone. After challenge with P. aeruginosa, PLGA-PopB/PcrH-immunized mice showed significantly lower bacterial counts in the lungs and improved survival. In conclusion, encapsulation of PopB/PcrH in PLGA nanoparticles can elicit Th17 responses to intranasal vaccination and protect mice against acute lethal P. aeruginosa pneumonia.
- Published
- 2018
13. Development of a Chimeric Vaccine Against Pseudomonas aeruginosa Based on the Th17-Stimulating Epitopes of PcrV and AmpC
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Jinning Wei, Xin Cheng, Quanming Zou, Jiang Gu, Chuang Wan, Liu-sheng Peng, Chen Gao, Dongshui Lu, Ping Luo, Hao Zeng, Yi Zhang, and Ying Wang
- Subjects
Pore Forming Cytotoxic Proteins ,lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Protective immunity ,Pseudomonas Vaccines ,Bacterial Toxins ,030106 microbiology ,Immunology ,Epitopes, T-Lymphocyte ,pulmonary infection ,chemical and pharmacologic phenomena ,Pulmonary infection ,Biology ,medicine.disease_cause ,beta-Lactamases ,Epitope ,Microbiology ,law.invention ,Mice ,03 medical and health sciences ,Bacterial Proteins ,Antigen ,law ,medicine ,Animals ,Immunology and Allergy ,Original Research ,Mice, Knockout ,Antigens, Bacterial ,Pseudomonas aeruginosa ,030104 developmental biology ,epitope analysis ,Immunization ,Recombinant DNA ,Th17 Cells ,Female ,Nasal administration ,chimeric vaccine ,Th17 responses ,lcsh:RC581-607 - Abstract
Pulmonary infection caused by Pseudomonas aeruginosa (PA) has created an urgent need for an efficient vaccine, but the protection induced by current candidates is limited, partially because of the high variability of the PA genome. Antigens targeting pulmonary Th17 responses are able to provide antibody-independent and broad-spectrum protection; however, little information about Th17-stimulating antigens in PA is available. Herein, we identified two novel PA antigens that effectively induce Th17-dependent protection, namely, PcrV (PA1706) and AmpC (PA4110). Compared to intramuscular immunization, intranasal immunization enhanced the protection of rePcrV due to activation of a Th17 response. The Th17-stimulating epitopes of PcrV and AmpC were identified, and the recombinant protein PVAC was designed and generated by combining these Th17-stimulating epitopes. PVAC was successfully produced in soluble form and elicited broad protective immunity against PA. Our results provide an alternative strategy for the development of Th17-based vaccines against PA and other pathogens.
- Published
- 2021
14. Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia
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Kelly L. Weaver, Aaron C. Malkowski, Catherine B. Blackwood, Justin R. Bevere, Emel Sen-Kilic, F. Heath Damron, William T. Witt, Annalisa B. Huckaby, Alexander M. Horspool, and Mariette Barbier
- Subjects
0301 basic medicine ,correlates of protection ,Pseudomonas Vaccines ,030106 microbiology ,Immunology ,whole-cell vaccine ,medicine.disease_cause ,Microbiology ,Mice ,03 medical and health sciences ,Immune system ,Adjuvants, Immunologic ,Pneumonia, Bacterial ,medicine ,Animals ,Humans ,Pseudomonas Infections ,Spotlight ,Pathogen ,biology ,Pseudomonas aeruginosa ,Vaccination ,Antibody titer ,vaccines ,Antibodies, Bacterial ,humoral immune response ,030104 developmental biology ,Infectious Diseases ,Immunization ,Microbial Immunity and Vaccines ,Models, Animal ,biology.protein ,Parasitology ,Antibody ,CD8 - Abstract
Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant microorganism., Pseudomonas aeruginosa is a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine against P. aeruginosa could help prevent infections caused by this highly antibiotic-resistant microorganism. We propose that identifying the vaccine-induced correlates of protection against P. aeruginosa will facilitate the development of a vaccine against this pathogen. In this study, we investigated the mechanistic correlates of protection of a curdlan-adjuvanted P. aeruginosa whole-cell vaccine (WCV) delivered intranasally. The WCV significantly decreased bacterial loads in the respiratory tract after intranasal P. aeruginosa challenge and raised antigen-specific antibody titers. To study the role of B and T cells during vaccination, anti-CD4, -CD8, and -CD20 depletions were performed prior to WCV vaccination and boosting. The depletion of CD4+, CD8+, or CD20+ cells had no impact on the bacterial burden in mock-vaccinated animals. However, depletion of CD20+ B cells, but not CD8+ or CD4+ T cells, led to the loss of vaccine-mediated bacterial clearance. Also, passive immunization with serum from WCV group mice alone protected naive mice against P. aeruginosa, supporting the role of antibodies in clearing P. aeruginosa. We observed that in the absence of T cell-dependent antibody production, mice vaccinated with the WCV were still able to reduce bacterial loads. Our results collectively highlight the importance of the humoral immune response for protection against P. aeruginosa and suggest that the production of T cell-independent antibodies may be sufficient for bacterial clearance induced by whole-cell P. aeruginosa vaccination.
- Published
- 2021
15. Construction of Genomic Library and High-Throughput Screening of Pseudomonas aeruginosa Novel Antigens for Potential Vaccines
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Wanting, Xu, Lei, Li, Xiaobin, Wen, Qun, Liu, Yan, Liu, Xingyong, Wang, Langhuan, Lei, Qiushan, Chen, and Li, Liu
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DNA, Bacterial ,Antigens, Bacterial ,Cross Infection ,Genomic Library ,Vaccines, Synthetic ,Pseudomonas Vaccines ,Antibodies, Bacterial ,Recombinant Proteins ,High-Throughput Screening Assays ,Disease Models, Animal ,Mice ,Immunogenicity, Vaccine ,Immunoglobulin G ,Pseudomonas aeruginosa ,Animals ,Humans ,Female ,Pseudomonas Infections - Abstract
Hospital-acquired infections with Pseudomonas aeruginosa have become a great challenge in caring for critically ill and immunocompromised patients. The cause of high mortality is the presence of multi-drug resistant (MDR) strains, which confers a pressing need for vaccines. Although vaccines against P. aeruginosa have been in development for more than several decades, there is no vaccine for patients at present. In this study, we purified genomic DNA of P. aeruginosa from sera of patients affected, constructed genome-wide library with random recombinants, and screened candidate protein antigens by evaluating their protective effects in vivo. After 13-round of screening, 115 reactive recombinants were obtained, among which 13 antigens showed strong immunoreactivity (more than 10% reaction to PcrV, a well-characterized V-antigen of P. aeruginosa). These 13 antigens were: PpiA, PtsP, OprP, CAZ10_34235, HmuU_2, PcaK, CarAd, RecG, YjiR_5, LigD, KinB, RtcA, and PscF. In vivo studies showed that vaccination with PscF protected against lethal P. aeruginosa challenge, and decreased lung inflammation and injury. A genomic library of P. aeruginosa could be constructed in this way for the first time, which could not only screen candidate antigens but also in a high-throughput way. PscF was considered as an ideal promising vaccine candidate for combating P. aeruginosa infection and was supported for further evaluation of its safety and efficacy.
- Published
- 2020
16. Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine
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Siobhán McClean, Maite Sainz-Mejías, and Irene Jurado-Martín
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0301 basic medicine ,Lipopolysaccharides ,Cystic Fibrosis ,virulence factors ,Review ,medicine.disease_cause ,Cystic fibrosis ,immune response ,Mice ,Pseudomonas aeruginosa ,ESKAPE ,host-pathogen interactions ,vaccine antigens ,adjuvants ,Vaccines, DNA ,Longitudinal Studies ,Pathogen ,lcsh:QH301-705.5 ,Lung ,Respiratory Tract Infections ,General Medicine ,Antimicrobial ,Antibodies, Bacterial ,3. Good health ,Flagella ,Pseudomonas Vaccines ,Alginates ,030106 microbiology ,Exotoxins ,03 medical and health sciences ,Antibiotic resistance ,Immune system ,Th2 Cells ,Antigen ,Adjuvants, Immunologic ,medicine ,Animals ,Humans ,Pseudomonas Infections ,Antigens ,business.industry ,Host (biology) ,Th1 Cells ,medicine.disease ,Immunity, Innate ,030104 developmental biology ,lcsh:Biology (General) ,Immunology ,Th17 Cells ,business - Abstract
Pseudomonas aeruginosa is a leading cause of chronic respiratory infections in people with cystic fibrosis (CF), bronchiectasis or chronic obstructive pulmonary disease (COPD), and acute infections in immunocompromised individuals. The adaptability of this opportunistic pathogen has hampered the development of antimicrobial therapies, and consequently, it remains a major threat to public health. Due to its antimicrobial resistance, vaccines represent an alternative strategy to tackle the pathogen, yet despite over 50 years of research on anti-Pseudomonas vaccines, no vaccine has been licensed. Nevertheless, there have been many advances in this field, including a better understanding of the host immune response and the biology of P. aeruginosa. Multiple antigens and adjuvants have been investigated with varying results. Although the most effective protective response remains to be established, it is clear that a polarised Th2 response is sub-optimal, and a mixed Th1/Th2 or Th1/Th17 response appears beneficial. This comprehensive review collates the current understanding of the complexities of P. aeruginosa-host interactions and its implication in vaccine design, with a view to understanding the current state of Pseudomonal vaccine development and the direction of future efforts. It highlights the importance of the incorporation of appropriate adjuvants to the protective antigen to yield optimal protection.
- Published
- 2020
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17. Multicomponent Pseudomonas aeruginosa Vaccines Eliciting Th17 Cells and Functional Antibody Responses Confer Enhanced Protection against Experimental Acute Pneumonia in Mice.
- Author
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Shaikh MOF, Schaefers MM, Merakou C, DiBlasi M, Bonney S, Liao T, Zurakowski D, Kehl M, Tabor DE, DiGiandomenico A, and Priebe GP
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- Mice, Animals, Pseudomonas Vaccines, Pseudomonas aeruginosa, Th17 Cells, Type III Secretion Systems, Antibody Formation, Antibodies, Bacterial, Bacterial Proteins, Immunoglobulin G, Immune Sera, Pseudomonas Infections prevention & control, Pneumonia
- Abstract
The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. aeruginosa type III secretion system protein, PopB, elicits a strong Th17 response in mice after intranasal (IN) immunization and confers antibody-independent protection against pneumonia in mice. In the current study, we evaluated the immunogenicity and protective efficacy in mice of the combination of PopB (purified with its chaperone protein PcrH) and OprF/I, an outer membrane hybrid fusion protein, compared with immunization with the proteins individually either by the intranasal (IN) or subcutaneous (SC) routes. Our results show that after vaccination, a Th17 recall response from splenocytes was detected only in mice vaccinated with PopB/PcrH, either alone or in combination with OprF/I. Mice immunized with the combination of PopB/PcrH and OprF/I had enhanced protection in an acute lethal P. aeruginosa pneumonia model, regardless of vaccine route, compared with mice vaccinated with either alone or adjuvant control. Immunization generated IgG titers against the vaccine proteins and whole P. aeruginosa cells. Interestingly, none of these antisera had opsonophagocytic killing activity, but antisera from mice immunized with vaccines containing OprF/I, had the ability to block IFN-γ binding to OprF/I, a known virulence mechanism. Hence, vaccines combining PopB/PcrH with OprF/I that elicit functional antibodies lead to a broadly and potently protective vaccine against P. aeruginosa pulmonary infections.
- Published
- 2022
- Full Text
- View/download PDF
18. Serum albumin nanoparticles vaccine provides protection against a lethal Pseudomonas aeruginosa challenge
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Luiz Gustavo de Almeida, Natalia Ingrid Oliveira Silva, Luiz Cosme Cotta Malaquias, Anna Carolina Toledo da Cunha Pereira, Stella Maria de Souza Morais, Luiz Felipe Leomil Coelho, Felipe Fornias Sperandio, Ezequiel Aparecido Salvador, Pedro Henrique Cruvinel da Silva, Matheus Pereira de Araújo, Raissa Prado Rocha, Gustavo Portela Ferreira, Patrick Veras Quelemes, Lorena Júnia de Souza Santos, Naiara Ferreira Rodigues, Olindo Assis Martins Filho, Isabella Rodrigues Franco, and Gabriel Augusto Pires de Souza
- Subjects
0301 basic medicine ,Pseudomonas Vaccines ,030106 microbiology ,Serum albumin ,Virulence ,medicine.disease_cause ,Cystic fibrosis ,Microbiology ,Mice ,03 medical and health sciences ,Blood serum ,Antigen ,medicine ,Animals ,Pseudomonas Infections ,Lung ,Pathogen ,Antigens, Bacterial ,General Veterinary ,General Immunology and Microbiology ,biology ,Pseudomonas aeruginosa ,business.industry ,Vaccination ,Public Health, Environmental and Occupational Health ,Serum Albumin, Bovine ,medicine.disease ,Antibodies, Bacterial ,Bacterial Load ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Blood chemistry ,biology.protein ,Cytokines ,Nanoparticles ,Molecular Medicine ,Female ,business - Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in immunocompromised individuals and in patients with cystic fibrosis. A range of vaccines to prevent infections caused by P. aeruginosa has already been tested, yet no vaccine against this pathogen is currently available. The goal of this study was to evaluate the potential of bovine serum albumin nanoparticles (BSA-NPs) associated with total P. aeruginosa ATCC 27853 antigens in inducing protection against the infection with virulent P. aeruginosa PA14 strain in murine model of nasal infection. Swiss mice were immunized with BSA-NPs associated with total P. aeruginosa antigens (NPPa) or empty NPs (NPe). As positive and negative control, groups of animals were immunized with total antigens of P. aeruginosa ATCC 27853 and phosphate buffered saline, respectively. Immunized mice were infected via nasal route using P. aeruginosa PA14 strain. The survival after 48 h was evaluated and the lungs from animals were processed for quantification of bacterial load, cytokine expression and histopathological analysis. After infection with P. aeruginosa PA14, animals immunized with NPPa had the highest survival rate, the lowest bacterial lung load, a controlled production of cytokines and few histopathological changes. These results indicate that NPPa immunization protected mice from infection, contributing for the elimination of the bacteria from the lungs, which consequently reflected the survival of the animals. Therefore, this vaccine was able to induce a functional response in an animal model of lethal infection and thereby is a promising platform for P. aeruginosa vaccines.
- Published
- 2018
19. Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa
- Author
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Ramadan Hassan, Abeer M. Abd El-Aziz, Mona I. Shaaban, Hany I. Kenawy, Wael El-Naggar, and Youssif M. Ali
- Subjects
0301 basic medicine ,lcsh:QR1-502 ,flagellin B ,medicine.disease_cause ,lcsh:Microbiology ,Mice ,outer membrane proteins ,Immunology and Allergy ,nonmucoid ,Cloning, Molecular ,Lung ,Respiratory Tract Infections ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,Vaccination ,Pseudomonas ,Antibody titer ,General Medicine ,Antibodies, Bacterial ,Infectious Diseases ,Pseudomonas aeruginosa ,Female ,Antibody ,Bacterial outer membrane ,Bacterial Outer Membrane Proteins ,Microbiology (medical) ,congenital, hereditary, and neonatal diseases and abnormalities ,Pseudomonas Vaccines ,Lipoproteins ,Recombinant Fusion Proteins ,030106 microbiology ,mucoid ,Microbiology ,03 medical and health sciences ,Bacterial Proteins ,Phagocytosis ,Pseudomonas infection ,Immunology and Microbiology(all) ,medicine ,Animals ,Pseudomonas Infections ,Opsonin ,General Immunology and Microbiology ,Gene Expression Regulation, Bacterial ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,medicine.disease ,digestive system diseases ,respiratory tract diseases ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Immunization ,Flagellin - Abstract
Background Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, which considered as a common cause of nosocomial infection and life-threatening complications in immunocompromized and cystic fibrosis patients. Here, we evaluate the protective effect of recombinant vaccines composed of outer membrane proteins OprF and OprI alone or in combination with flagellin B against mucoid and nonmucoid pseudomonas infection. Methods BALB/C mice were immunized subcutaneous using OprF and OprI with or without flagellin B and antibody titers were determined. Serum bactericidal and opsonophagocytosis activities of immunized and control sera were estimated against mucoid and nonmucoid pseudomonas strains. Lung tissue sections from immunized and nonimmunized mice were analyzed and the levels of peripheral neutrophils infiltration into the lung and tissue inflammation were scored. Results Subcutaneous immunization using OprF and OprI with or without flagellin B elicited higher antibody titers against OprF, OprI, and flagellin B. The produced antibodies successfully opsonized both mucoid and nonmucoid strains with subsequent activation of the terminal pathway of complement that enhances killing of nonmucoid strains via complement-mediated lysis. Furthermore, opsonized mucoid and nonmucoid strains showed enhanced opsonophagocytosis via human peripheral neutrophils, a mechanism that kills P. aeruginosa when complement mediated lysis is not effective especially with mucoid strains. Immunized mice also showed a significant prolonged survival time, lower bacteremia, and reduced lung damage when compared with control nonimmunized mice. Conclusion Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa .
- Published
- 2018
20. Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach
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Saadia Andleeb, Muhammad Ibrahim Rashid, Amjad Ali, and Anam Naz
- Subjects
0301 basic medicine ,Penicillin binding proteins ,Pseudomonas Vaccines ,Pseudomonas aeruginosa ,Reverse vaccinology ,Genomics ,Drug resistance ,Biology ,Proteomics ,medicine.disease_cause ,Epitope ,Microbiology ,Epitopes ,03 medical and health sciences ,030104 developmental biology ,Bacterial Proteins ,Drug Design ,Vaccines, Subunit ,Genetics ,Peptide vaccine ,medicine ,Humans ,Pseudomonas Infections - Abstract
Pseudomonas aeruginosa is among top critical nosocomial infectious agents due to its persistent infections and tendency for acquiring drug resistance mechanisms. To date, there is no vaccine available for this pathogen. We attempted to exploit the genomic and proteomic information of P. aeruginosa though reverse-vaccinology approaches to unveil the prospective vaccine candidates. P. aeruginosa strain PAO1 genome was subjected to sequential prioritization approach following genomic, proteomics and structural analyses. Among, the predicted vaccine candidates: surface components of antibiotic efflux pumps (Q9HY88, PA2837), chaperone-usher pathway components (CupC2, CupB3), penicillin binding protein of bacterial cell wall (PBP1a/mrcA), extracellular component of Type 3 secretory system (PscC) and three uncharacterized secretory proteins (PA0629, PA2822, PA0978) were identified as potential candidates qualifying all the set criteria. These proteins were then analyzed for potential immunogenic surface exposed epitopes. These predicted epitopes may provide a basis for development of a reliable subunit vaccine against P. aeruginosa.
- Published
- 2017
21. Preparation of Pseudomonas aeruginosa alginate-flagellin immunoconjugate
- Author
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Iraj Nikokar, Korosh Khanaki, Sobhan Faezi, Gholamreza Goudarzi, Seyed Davar Siadat, Soroush Sardari, Mehdi Mahdavi, Ahmad Reza Bahrmand, and Ebrahim Mirzajani
- Subjects
0301 basic medicine ,Immunoconjugates ,Pseudomonas Vaccines ,Bioengineering ,Biology ,medicine.disease_cause ,Applied Microbiology and Biotechnology ,Microbiology ,Mice ,03 medical and health sciences ,Conjugate vaccine ,medicine ,Animals ,Pseudomonas Infections ,Opsonin ,Pharmacology ,Antiserum ,Mice, Inbred BALB C ,General Immunology and Microbiology ,Pseudomonas aeruginosa ,Immunogenicity ,General Medicine ,Immunoconjugate ,Titer ,030104 developmental biology ,Female ,Flagellin ,Biotechnology ,Conjugate - Abstract
Mucoid strains of Pseudomonas aeruginosa are closely associated with chronic pulmonary infections. In this report we describe a straightforward approach to conjugate high molecular weight alginate to type b-flagellin (FLB) and investigation of its bioactivity. The conjugation process was performed by using ADH and EDAC. The endotoxin was eliminated from the candidate vaccine by LPS removal resin followed by LAL test. The bioconjugate molecules were verified by simultaneously determination of polysaccharide/protein content followed by gel filtration chromatography and FTIR spectroscopy. Groups of eight BALB/c mice were injected intranasally with 5 μg (per each nostril) of purified alginate, FLB and conjugated alginate-FLB with two week intervals. The functional activity of the vaccine was evaluated by ELISA and opsonophagocytosis tests. Vaccination with the alginate-FLB conjugate induced a significant (P = 0.0033) rise in alginate specific IgG in mice. At all dilution ranges, the opsonic activity of the conjugate vaccine antisera was significantly higher than alginate alone (61.9% vs. 17.3% at 1:4 dilution; P = 0.0067). The alginate-FLB conjugate could elicit high specific antibodies titer against alginate by improving its immunogenicity. In addition, the antisera raised against conjugate vaccine act as a suitable opsonin for phagocytosis of the mucoid strains of P. aeruginosa.
- Published
- 2017
22. [Construction of recombinant Bb(pGEX-OprF-I) vaccine of Pseudomonas aeruginosa and its protection elicited in mice]
- Author
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Chengcheng, Liang and Wengui, Li
- Subjects
Mice ,Mice, Inbred BALB C ,Random Allocation ,Bacterial Proteins ,Pseudomonas Vaccines ,Lipoproteins ,Recombinant Fusion Proteins ,Pseudomonas aeruginosa ,Animals ,Pseudomonas Infections ,Bifidobacterium bifidum - Abstract
Objective To construct and identify Bifidobacterium bifidum-vectored outer membrane protein F-I[rBb(pGEX-OprF-I)] vaccine of Pseudomonas aeruginosa and observe its protection against Pseudomonas aeruginosa infection in mice. Methods OprF and OprI genes were amplified by PCR, then the OprF-I fusion gene obtained by gene SOEing was digested and ligated into the vector pGEX-1λT to construct the recombinant plasmid pGEX-OprF-I. The plasmid was transformed into Bifidobacterium bifidum (Bb) by electroporation, and the rBb(pGEX-OprF-I) vaccine was constructed and identified by double enzyme digestion and PCR. Expression products of the vaccine induced by IPTG were analyzed and identified by SDS-PAGE and Western blot analysis. Twenty-one BALB/c mice were randomly divided into rBb(pGEX-OprF-I) vaccine group, Bb-pGEX-1λT empty vector group and Bb control group. The 5×10
- Published
- 2019
23. Immunopotentiation of the engineered low-molecular-weight pilin targeting Pseudomonas aeruginosa: A combination of immunoinformatics investigation and active immunization
- Author
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Mehdi Mahdavi, Alireza Salimi Chirani, Yasaman Ahmadbeigi, Mehdi Goudarzi, and Neda Soleimani
- Subjects
0301 basic medicine ,Immunogen ,Pseudomonas Vaccines ,Immunology ,Fimbria ,Virulence ,Epitopes, T-Lymphocyte ,Active immunization ,medicine.disease_cause ,Epitope ,Pilus ,Microbiology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Bacterial Proteins ,medicine ,Animals ,Pseudomonas Infections ,Molecular Biology ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,Pseudomonas aeruginosa ,Immunodominant Epitopes ,Vaccination ,Computational Biology ,030104 developmental biology ,Pilin ,biology.protein ,Epitopes, B-Lymphocyte ,Female ,030215 immunology - Abstract
Several vaccine candidates have been introduced for immunization against Pseudomonas aeruginosa strains. Despite extensive efforts in recent decades, there is no accurate immunogenic candidate against this pathogen in the market yet. Due to the rapid increase in several drug-resistant strains, P. aeruginosa has caused various health concerns worldwide. It encodes many specific virulence features, which can be used as an appropriate vaccine candidate. The primary stage of the pathogenesis of P. aeruginosa is the expression of many dynamic adhesive molecules, such as type IV pili (T4P), which acts as a principal colonization factor. It has been confirmed that three different subtypes of T4P, including type IVa (T4aP), type IVb (T4bP) and tight adherence (Tad) pili are expressed by P. aeruginosa. The IVa fimbriae type is almost the main cause of challenges to design an effective pili based-immunotherapy method. Nevertheless, in terms of heterogeneity, variability and hidden conserved binding site of T4aP, this attitude has been remained controversial and there is no permitted human study based on IVa pilin commercially. The engineered synthetic peptide-based vaccines are highly talented to mimic the target. In this research, for the first time, some dominant immunogenic features of the Flp protein, such as both B- and T-cell-associated epitopes, presence of IgE-associated epitopes, solvent-accessible surface area were evaluated by analytical immunoinformatics methods. In addition, we designed the engineered Flp pilin as an effective immunogenic substance against several clinically important P. aeruginosa strains. Moreover, by practical active immunization approaches, the humoral and cellular immune response against the extremely conserved region of the engineered synthetic Flp (EFlp) formulated in Montanide ISA 266 compared to the control group. The results of active immunization against EFlp significantly signified that EFlp-Montanide ISA 266 (EFLP-M) strongly could induce both humoral and cellular immune responses. We concluded that Flp pilin has therapeutic potential against numerous clinically significant P. aeruginosa strains and can be served as a novel immunogen for further investigations for development of effective immunotherapy methods against P. aeruginosa as a dexterous pathogen.
- Published
- 2019
24. Emerging therapies against infections with
- Author
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Burkhard, Tümmler
- Subjects
Cross Infection ,phage therapy ,Drug Development ,Pseudomonas Vaccines ,ß-lactam inhibitor ,antibiotic ,vaccine ,Pseudomonas aeruginosa ,Humans ,Pseudomonas Infections ,Review ,Articles ,Anti-Bacterial Agents - Abstract
Infections with Pseudomonas aeruginosa have been marked with the highest priority for surveillance and epidemiological research on the basis of parameters such as incidence, case fatality rates, chronicity of illness, available options for prevention and treatment, health-care utilization, and societal impact. P. aeruginosa is one of the six ESKAPE pathogens that are the major cause of nosocomial infections and are a global threat because of their capacity to become increasingly resistant to all available antibiotics. This review reports on current pre-clinical and clinical advances of anti-pseudomonal therapies in the fields of drug development, antimicrobial chemotherapy, vaccines, phage therapy, non-bactericidal pathoblockers, outer membrane sensitizers, and host defense reinforcement.
- Published
- 2019
25. Intranasal Peptide-Based FpvA-KLH Conjugate Vaccine Protects Mice From
- Author
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Emel Sen-Kilic, Catherine B. Blackwood, Dylan T. Boehm, William T. Witt, Aaron C. Malkowski, Justin R. Bevere, Ting Y. Wong, Jesse M. Hall, Shelby D. Bradford, Melinda E. Varney, Fredrick Heath Damron, and Mariette Barbier
- Subjects
0301 basic medicine ,medicine.medical_treatment ,medicine.disease_cause ,cystic fibrosis ,Mice ,0302 clinical medicine ,infection and immunity ,vaccine ,Immunology and Allergy ,Medicine ,Original Research ,peptide-based vaccines ,biology ,Immunogenicity ,hemic and immune systems ,Antibodies, Bacterial ,Recombinant Proteins ,3. Good health ,Vaccination ,Memory, Short-Term ,Pseudomonas aeruginosa ,Vaccines, Subunit ,Cytokines ,Female ,Adjuvant ,Bacterial Outer Membrane Proteins ,lcsh:Immunologic diseases. Allergy ,Pseudomonas Vaccines ,Immunology ,chemical and pharmacologic phenomena ,complex mixtures ,FpvA ,03 medical and health sciences ,Immune system ,Conjugate vaccine ,Pneumonia, Bacterial ,Animals ,Humans ,Pseudomonas Infections ,Immunity, Mucosal ,Administration, Intranasal ,iron acquisition ,Vaccines, Conjugate ,business.industry ,Disease Models, Animal ,030104 developmental biology ,Immunization ,Hemocyanins ,biology.protein ,mucosal immunity ,business ,lcsh:RC581-607 ,Keyhole limpet hemocyanin ,030215 immunology - Abstract
Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against P. aeruginosa before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against P. aeruginosa, we formulated a novel peptide-based P. aeruginosa subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and challenge model. Immunization with the FpvA-KLH vaccine decreased the bacterial burden and lung edema after P. aeruginosa challenge. Vaccination with FpvA-KLH lead to antigen-specific IgG and IgM antibodies in sera, and IgA antibodies in lung supernatant. FpvA-KLH immunized mice had an increase in recruitment of CD11b+ dendritic cells as well as resident memory CD4+ T cells in the lungs compared to non-vaccinated challenged mice. Splenocytes isolated from vaccinated animals showed that the FpvA-KLH vaccine with the adjuvant curdlan induces antigen-specific IL-17 production and leads to a Th17 type of immune response. These results indicate that the intranasal FpvA-KLH conjugate vaccine can elicit both mucosal and systemic immune responses. These observations suggest that the intranasal peptide-based FpvA-KLH conjugate vaccine with curdlan is a potential vaccine candidate against P. aeruginosa pneumonia.
- Published
- 2019
26. Genome-Based Approach Delivers Vaccine Candidates Against Pseudomonas aeruginosa
- Author
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Irene Bianconi, Beatriz Alcalá-Franco, Maria Scarselli, Mattia Dalsass, Scilla Buccato, Annalisa Colaprico, Sara Marchi, Vega Masignani, and Alessandra Bragonzi
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Cystic Fibrosis ,Pseudomonas Vaccines ,mouse model ,Immunology ,Hypothetical protein ,Biology ,medicine.disease_cause ,Microbiology ,Mouse model ,03 medical and health sciences ,Mice ,Open Reading Frames ,0302 clinical medicine ,Antibiotic resistance ,reverse vaccinology ,Antigen ,respiratory infection ,Respiratory infection ,vaccine ,medicine ,Immunology and Allergy ,Animals ,Humans ,Pseudomonas Infections ,Antigens ,Genome ,Pseudomonas aeruginosa ,Animal ,Reverse vaccinology ,Bacterial ,Genomics ,Acquired immune system ,Vaccination ,030104 developmental biology ,Disease Models ,Vaccine ,Antigens, Bacterial ,Disease Models, Animal ,Genome-Wide Association Study ,Genome, Bacterial ,lcsh:RC581-607 ,030215 immunology - Abstract
High incidence, severity and increasing antibiotic resistance characterize Pseudomonas aeruginosa infections, highlighting the need for new therapeutic options. Vaccination strategies to prevent or limit P. aeruginosa infections represent a rational approach to positively impact the clinical outcome of risk patients; nevertheless this bacterium remains a challenging vaccine target. To identify novel vaccine candidates, we started from the genome sequence analysis of the P. aeruginosa reference strain PAO1 exploring the reverse vaccinology approach integrated with additional bioinformatic tools. The bioinformatic approaches resulted in the selection of 52 potential antigens. These vaccine candidates were conserved in P. aeruginosa genomes from different origin and among strains isolated longitudinally from cystic fibrosis patients. To assess the immune-protection of single or antigens combination against P. aeruginosa infection, a vaccination protocol was established in murine model of acute respiratory infection. Combinations of selected candidates, rather than single antigens, effectively controlled P. aeruginosa infection in the in vivo model of murine pneumonia. Five combinations were capable of significantly increase survival rate among challenged mice and all included PA5340, a hypothetical protein exclusively present in P. aeruginosa. PA5340 combined with PA3526-MotY gave the maximum protection. Both proteins were surface exposed by immunofluorescence and triggered a specific immune response. Combination of these two protein antigens could represent a potential vaccine to prevent P. aeruginosa infection.
- Published
- 2019
27. Rational Design of a Chimeric Derivative of PcrV as a Subunit Vaccine Against
- Author
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Chuang, Wan, Jin, Zhang, Liqun, Zhao, Xin, Cheng, Chen, Gao, Ying, Wang, Wanting, Xu, Quanming, Zou, and Jiang, Gu
- Subjects
Pore Forming Cytotoxic Proteins ,Antigens, Bacterial ,Pseudomonas Vaccines ,Immunodominant Epitopes ,Bacterial Toxins ,Immunology ,rational design ,Disease Models, Animal ,Mice ,T-Lymphocyte Subsets ,Cell Line, Tumor ,vaccine ,Pseudomonas aeruginosa ,Vaccines, Subunit ,PcrV ,Animals ,pneumonia ,Female ,Pseudomonas Infections ,Original Research - Abstract
Pseudomonas aeruginosa (PA) is a major cause of nosocomial infections, which remain an unsolved problem in the clinic despite conventional antibiotic treatment. A PA vaccine could be both an effective and economical strategy to address this issue. Many studies have shown that PcrV, a structural protein of the type 3 secretion system (T3SS) from PA, is an ideal target for immune prevention and therapy. However, difficulties in the production of high-quality PcrV likely hinder its further application in the vaccine industry. Thus, we hypothesized that an optimized PcrV derivative with a rational design could be produced. In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-PcrVNH antibodies alone also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. These results provide an additional example for the rational design of antigens and suggest that PcrVNH is a promising vaccine candidate for the control of PA infection.
- Published
- 2018
28. Progress Toward the Elusive
- Author
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Christina, Merakou, Matthew M, Schaefers, and Gregory P, Priebe
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Clinical Trials as Topic ,Drug Development ,Pseudomonas Vaccines ,Pseudomonas aeruginosa ,Drug Evaluation, Preclinical ,Animals ,Humans ,Th17 Cells ,Pseudomonas Infections ,Antibodies, Bacterial - Published
- 2018
29. Intranasal Delivery of Antigen-Coated Polymer Particles Protects against Pseudomonas aeruginosa Infection.
- Author
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Gonzaga ZJC, Zhang J, and Rehm BHA
- Subjects
- Aluminum Hydroxide, Animals, Antibodies, Bacterial, Epitopes, Mice, Polymers, Pseudomonas Vaccines, Pseudomonas aeruginosa metabolism, Pseudomonas Infections prevention & control
- Abstract
Pseudomonas aeruginosa is an opportunistic human pathogen that is intrinsically resistant to multiple antibiotics, causing severe and persistent infections in immunocompromised individuals. This bacterium has been listed as a priority pathogen by the WHO in 2017, and there is no vaccine available for human use. In this study, 10 vaccine candidate antigens were selected for particulate vaccine design. We engineered Escherichia coli to assemble biopolymer particles (BPs) that were either coated with epitopes (Ag) derived from OprF/I-AlgE proteins or PopB or PopB-Ag or coated with single or double copies of epitopes (10Ag and 10Ag(2x)) derived from OprF, OprI, AlgE, OprL, PopB, PilA, PilO, FliC, Hcp1, and CdrA. Antigen-coated BPs showed a diameter of 0.93-1.16 μm with negative surface charge. Antigens attached to BPs were identified by mass spectrometry. Vaccination with BP-Ag, BP-PopB, BP-PopBAg, PB-10Ag, and BP-10Ag(2x) with and without Alhydrogel adjuvant induced significant antigen-specific humoral and cell-mediated immune responses in mice. All particulate vaccines with Alhydrogel induced protection in an acute pneumonia murine model of P. aeruginosa infection, contributing to up to 80% survival when administered intramuscularly, and the addition of Alhydrogel boosted immunity. The BP-10Ag(2x) vaccine candidate showed the best performance and even induced protective immunity in the absence of Alhydrogel. Intramuscular administration of the BP-10Ag(2x) without Alhydrogel vaccine resulted in 60% survival. Intranasal vaccination induced immunity, contributing to about 90% survival. Overall, our data suggest that vaccination with BPs coated with P. aeruginosa antigens induce protective immunity against P. aeruginosa infections. The possibility of intranasal delivery will strongly facilitate administration and use of BP vaccines.
- Published
- 2022
- Full Text
- View/download PDF
30. A trivalent vaccine consisting of 'flagellin A+B and pilin' protects against Pseudomonas aeruginosa infection in a murine burn model
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Mohammad Javad Fatemi, Gholamreza Irajian, Fatemeh Korpi, Bahador Behrouz, Farhad B. Hashemi, and Parisa Laghaei
- Subjects
0301 basic medicine ,Pseudomonas Vaccines ,030106 microbiology ,medicine.disease_cause ,Microbiology ,Pilus ,Mice ,03 medical and health sciences ,Antigen ,medicine ,Animals ,Pseudomonas Infections ,biology ,Pseudomonas aeruginosa ,Vaccination ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Immunization ,Pilin ,Wound Infection ,biology.protein ,bacteria ,Fimbriae Proteins ,Antibody ,Burns ,Flagellin - Abstract
Pseudomonas aeruginosa is a common nosocomial pathogen in burn patients, and rapidly achieves antibiotic resistance, and thus, developing an effective vaccine is critically important for combating P. aeruginosa infection. Flagella and pili play important roles in colonization of P. aeruginosa at the burn wound site and its subsequent dissemination to deeper tissue and organs. In the present study, we evaluated protective efficacy of a trivalent vaccine containing flagellins A and B (FlaA + FlaB) + pilin (PilA) in a murine burn model of infection. “FlaA + FlaB + PilA” induced greater protection in P. aeruginosa murine burn model than the single components alone, and it showed broad immune protection against P. aeruginosa strains. Immunization with “FlaA + FlaB + PilA” induced strong opsonophagocytic antibodies and resulted in reduced bacterial loads, systemic IL-12/IL-10 cytokine expression, and increased survival after challenge with three times lethal dose fifty (LD50) of P. eruginosa strains. Moreover, the protective efficacy of “FlaA + FlaB + PilA” vaccination was largely attributed to specific antibodies. Taken together, these data further confirm that the protective effects of “FlaA + FlaB + PilA” vaccine significantly enhance efficacy compared with antibodies against either mono or divalent antigen, and that the former broadens the coverage against P. eruginosa strains that express two of the three antigens.
- Published
- 2020
31. Genome-Based Approach Delivers Vaccine Candidates Against
- Author
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Irene, Bianconi, Beatriz, Alcalá-Franco, Maria, Scarselli, Mattia, Dalsass, Scilla, Buccato, Annalisa, Colaprico, Sara, Marchi, Vega, Masignani, and Alessandra, Bragonzi
- Subjects
Antigens, Bacterial ,Cystic Fibrosis ,Pseudomonas Vaccines ,mouse model ,Immunology ,Genomics ,Disease Models, Animal ,Mice ,Open Reading Frames ,reverse vaccinology ,respiratory infection ,vaccine ,Pseudomonas aeruginosa ,Animals ,Humans ,Pseudomonas Infections ,Genome, Bacterial ,Genome-Wide Association Study ,Original Research - Abstract
High incidence, severity and increasing antibiotic resistance characterize Pseudomonas aeruginosa infections, highlighting the need for new therapeutic options. Vaccination strategies to prevent or limit P. aeruginosa infections represent a rational approach to positively impact the clinical outcome of risk patients; nevertheless this bacterium remains a challenging vaccine target. To identify novel vaccine candidates, we started from the genome sequence analysis of the P. aeruginosa reference strain PAO1 exploring the reverse vaccinology approach integrated with additional bioinformatic tools. The bioinformatic approaches resulted in the selection of 52 potential antigens. These vaccine candidates were conserved in P. aeruginosa genomes from different origin and among strains isolated longitudinally from cystic fibrosis patients. To assess the immune-protection of single or antigens combination against P. aeruginosa infection, a vaccination protocol was established in murine model of acute respiratory infection. Combinations of selected candidates, rather than single antigens, effectively controlled P. aeruginosa infection in the in vivo model of murine pneumonia. Five combinations were capable of significantly increase survival rate among challenged mice and all included PA5340, a hypothetical protein exclusively present in P. aeruginosa. PA5340 combined with PA3526-MotY gave the maximum protection. Both proteins were surface exposed by immunofluorescence and triggered a specific immune response. Combination of these two protein antigens could represent a potential vaccine to prevent P. aeruginosa infection.
- Published
- 2018
32. The protective effects of nasal PcrV-CpG oligonucleotide vaccination against Pseudomonas aeruginosa pneumonia
- Author
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Yoshifumi, Naito, Saeko, Hamaoka, Mao, Kinoshita, Atsushi, Kainuma, Masaru, Shimizu, Hideya, Katoh, Kiyoshi, Moriyama, Ken J, Ishii, and Teiji, Sawa
- Subjects
Male ,Pore Forming Cytotoxic Proteins ,Antigens, Bacterial ,Pseudomonas Vaccines ,Recombinant Fusion Proteins ,Bacterial Toxins ,Vaccination ,Pneumonia ,Antibodies, Bacterial ,Body Temperature ,Survival Rate ,Disease Models, Animal ,Mice ,Adjuvants, Immunologic ,Oligodeoxyribonucleotides ,Pseudomonas aeruginosa ,Type III Secretion Systems ,Animals ,Edema ,Pseudomonas Infections ,Lung ,Peroxidase - Abstract
An effective vaccine against Pseudomonas aeruginosa would be hugely beneficial to people who are susceptible to the serious infections it can cause. Vaccination against PcrV of the P. aeruginosa type III secretion system is a potential prophylactic strategy for improving the incidence and prognosis of P. aeruginosa pneumonia. Here, the effect of nasal PcrV adjuvanted with CpG oligodeoxynucleotide (CpG) was compared with a nasal PcrV/aluminum hydroxide gel (alum) vaccine. Seven groups of mice were vaccinated intranasally with one of the following: 1, PcrV-CpG; 2, PcrV-alum; 3, PcrV alone; 4, CpG alone; 5, alum alone; 6 and 7, saline control. Fifty days after the first immunization, anti-PcrV IgG, IgA and IgG isotype titers were measured; significant increases in these titers were detected only in the PcrV-CpG vaccinated mice. The vaccinated mice were then intratracheally infected with a lethal dose of P. aeruginosa and their body temperatures and survival monitored for 24 hr, edema, bacteria, myeloperoxidase activity and lung histology also being evaluated at 24 hr post-infection. It was found that 73% of the PcrV-CpG-vaccinated mice survived, whereas fewer than 30% of the mice vaccinated with PcrV-alum or adjuvant alone survived. Lung edema and other inflammation-related variables were less severe in the PcrV-CpG group. The significant increase in PcrV-specific IgA titers detected following PcrV-CpG vaccination is probably a component of the disease protection mechanism. Overall, our data show that intranasal PcrV-CpG vaccination has potential efficacy for clinical application against P. aeruginosa pneumonia.
- Published
- 2018
33. A facile approach for development of a vaccine made of bacterial double-layered membrane vesicles (DMVs)
- Author
-
Sihan Wang, Mo Li, Jin Gao, Zhenjia Wang, and Liguo Wang
- Subjects
0301 basic medicine ,Biodistribution ,Pseudomonas Vaccines ,T-Lymphocytes ,Biophysics ,Bioengineering ,Adaptive Immunity ,medicine.disease_cause ,Article ,Microbiology ,Biomaterials ,Sepsis ,03 medical and health sciences ,Mice ,Immune system ,Antibiotic resistance ,medicine ,Animals ,Pseudomonas Infections ,B-Lymphocytes ,Pseudomonas aeruginosa ,Chemistry ,Cell Membrane ,Dendritic Cells ,Acquired immune system ,medicine.disease ,Vaccination ,030104 developmental biology ,Membrane protein ,Mechanics of Materials ,Ceramics and Composites ,Cytokines ,Nanoparticles ,Bacterial Outer Membrane Proteins - Abstract
Bacterial infections cause acute and chronic diseases. Antimicrobial resistance and aging-related immune weakness remain challenging in therapy of infectious diseases. Vaccines are however an alternative to prevent bacterial infections. Here we report a facile method to rapidly generate bacterium-membrane-formed nanovesicles as a vaccine using nitrogen cavitation. The vaccine is comprised of double-layered membrane vesicles (DMVs) characterized by cryo-TEM, biochemistry and proteomics, showing DMVs possess the integrity of bacterial membrane and contain a wide range of membrane proteins required for vaccination. In the mouse sepsis model induced by Pseudomonas aeruginosa, we found that DMVs can improve mouse survival after mice were immunized with DMVs. The increased adaptive immunity and unique biodistribution of DMVs were responsible for enhanced protection of bacterial infection. Our studies demonstrate that this simple and innovative approach using nitrogen cavitation would be a promising technology for vaccine developments.
- Published
- 2018
34. [Study on Construction of Recombinant Bb-pGEX
- Author
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Xiao, Liu, Wen-Gui, Li, and Guang-Xu, Luo
- Subjects
Vaccines, Synthetic ,Pseudomonas Vaccines ,Lipoproteins ,Recombinant Fusion Proteins ,Immunoglobulin E ,Antibodies, Bacterial ,Immunity, Humoral ,Mice ,Random Allocation ,Bacterial Proteins ,Immunoglobulin G ,Pseudomonas aeruginosa ,Animals ,Pseudomonas Infections - Abstract
To construct the recombinant Bb-pGEX-TheTheThe recombinant Bb-pGEX
- Published
- 2018
35. Construction of a Protective Vaccine Against Lipopolysaccharide-Heterologous
- Author
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Chang, Liu, Xiaolei, Pan, Bin, Xia, Fei, Chen, Yongxin, Jin, Fang, Bai, Gregory, Priebe, Zhihui, Cheng, Shouguang, Jin, and Weihui, Wu
- Subjects
Lipopolysaccharides ,Pseudomonas Vaccines ,Virulence ,Immunology ,Gene Expression ,immunization ,Antibodies, Bacterial ,Disease Models, Animal ,Mice ,Bacterial Proteins ,Phagocytosis ,vaccine ,Pseudomonas aeruginosa ,Escherichia coli ,Pneumonia, Bacterial ,OprH ,outer membrane proteins ,Animals ,Humans ,Female ,Pseudomonas Infections ,Bacterial Outer Membrane Proteins ,Original Research - Abstract
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen, which causes infectious disease in patients with cystic fibrosis and compromised immunity. P. aeruginosa is difficult to eradicate because of its intrinsic resistance to most traditional antibiotics as well as acquired resistance mechanisms after decades of antibiotic usage. A full understanding of the P. aeruginosa pathogenesis mechanisms is necessary for the development of novel prevention and treatment strategies. To identify novel vaccine candidates, here we comprehensively examined the expression levels of all the known outer membrane proteins in two P. aeruginosa strains in a murine acute pneumonia model. OprH was one of the most highly expressed proteins during infection. In addition, OprH is known to be highly immunogenic and accessible by host proteins. Thus, it was chosen as a vaccine candidate. To further identify vaccine candidates, 34 genes highly expressed during infection were evaluated for their contributions in virulence by testing individual transposon insertion mutants. Among them, fpvA, hasR, and foxA were found essential for bacterial virulence and therefore included in vaccine construction. Immunization with a mixture of FpvA, HasR, and FoxA rendered no protection, however, while immunization by OprH refolded in liposomes elicited specific opsonic antibodies and conferred protection against two lipopolysaccharide-heterologous P. aeruginosa strains (PA14 and PA103). Overall, by studying the expression profile of the P. aeruginosa outer membrane proteins during infection, we identified OprH as a potential vaccine candidate for the prevention of lung infection by P. aeruginosa.
- Published
- 2017
36. Immunological evaluation of an alginate-based conjugate as a vaccine candidate againstPseudomonas aeruginosa
- Author
-
Hashem Khorsand Mohammadpour, Ali Farjah, Seyed Davar Siadat, Seyed Fazlollah Mousavi, Mehdi Shafiee Ardestani, and Parviz Owlia
- Subjects
Microbiology (medical) ,Cystic Fibrosis ,Pseudomonas Vaccines ,Alginates ,Drug resistance ,Neisseria meningitidis, Serogroup B ,medicine.disease_cause ,Pathology and Forensic Medicine ,Microbiology ,Mice ,Immune system ,Glucuronic Acid ,Conjugate vaccine ,Drug Resistance, Bacterial ,medicine ,Animals ,Immunology and Allergy ,Pseudomonas Infections ,Mice, Inbred BALB C ,Vaccines, Conjugate ,biology ,Pseudomonas aeruginosa ,Hexuronic Acids ,Neisseria meningitidis ,Immunogenicity ,Cell Membrane ,Vaccination ,General Medicine ,Antibodies, Bacterial ,Virology ,Bacterial Load ,Immunoglobulin G ,biology.protein ,Antibody - Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, is usually resistant to antimicrobialagents, and is the leading cause of morbidity and premature mortality in patients with cystic fibrosis (CF). Mucoidstrains of P. aeruginosa produce a virulence factor known as alginate. Developing a strategy to raise opsonic antibodiesagainst alginate could be promising for the treatment of P. aeruginosa infection in CF patients. Conjugation of alginateto a carrier protein is a good method for increasing the immunogenicity of alginate. We conjugated alginate to theouter membrane vesicle (OMV) of Neisseria meningitidis serogroup B, which is a safe carrier protein, and evaluated itsefficacy in mice. To evaluate the immune response, total IgG, IgG1, IgG2a, and IgG2b titers were analyzed. Immuniza-tion of mice with the alginate–OMV conjugate raised the levels of opsonic antibodies, and the vaccinated mice wereprotected when challenged intranasally with P. aeruginosa. Further studies showed that the conjugated vaccine couldeliminate P. aeruginosa from the lungs of infected mice. This study supports the proposal that immunization of micewith an alginate–OMV conjugate vaccine could be safe and protective against P. aeruginosa infection.Key words: Pseudomonas aeruginosa; alginate; conjugate vaccine.Parviz Owlia, Molecular Microbiology Research Center, Shahed University, Tehran, Iran. e-mail: owlia@yahoo.com
- Published
- 2014
37. Immunogenicity of a 24-Valent Klebsiella Capsular Polysaccharide Vaccine and an Eight-Valent Pseudomonas O-Polysaccharide Conjugate Vaccine Administered to Victims of Acute Trauma
- Author
-
Stanley J. Cryz, Wayne N. Campbell, Elizabeth Hendrix, and Alan S. Cross
- Subjects
Microbiology (medical) ,Adult ,Male ,Klebsiella ,Adolescent ,Pseudomonas Vaccines ,Klebsiella pneumoniae ,Bacterial Toxins ,Active immunization ,Polysaccharide Vaccine ,Microbiology ,Conjugate vaccine ,Pseudomonas ,Medicine ,Humans ,Pseudomonas Infections ,Vaccines, Conjugate ,biology ,business.industry ,Immunogenicity ,Polysaccharides, Bacterial ,Vaccination ,O Antigens ,biology.organism_classification ,Antibodies, Bacterial ,Klebsiella Infections ,Infectious Diseases ,Blunt trauma ,Immunoglobulin G ,Immunology ,Bacterial Vaccines ,Wounds and Injuries ,Female ,Safety ,business - Abstract
We measured the antibody response in 10 victims of acute blunt trauma and penetrating trauma who were immunized against Klebsiella pneumoniae and Pseudomonas species within 72 hours of injury. The two vaccines, which were previously shown to be safe and immunogenic in uninjured humans, were a 24-valent K. pneumoniae capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide-toxin A conjugate vaccine. The patients were between 18 and 44 years of age, had Injury Severity Scores that ranged between 9 and 34, and did not have chronic infections or malignancies. On days 14 and 28 after immunization, all patients had a response of greater than fourfold to at least six of the nine Pseudomonas vaccine antigens. Half of the patients responded to eight of the nine antigens. Nine patients responded to at least 18 of 24 Klebsiella antigens, and seven patients responded to 22 of the 24 antigens. No important side effects were attributed to the vaccines. The results of this preliminary study indicate that active immunization against potential pathogens is possible in victims of acute trauma.
- Published
- 2017
38. Increased Immunogenicity and Protective Efficacy of a
- Author
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Ji In, Ryu, Seo Ri, Wui, Ara, Ko, Yeon Jeong, Lee, Hien, Do, Hark Jun, Kim, In Moo, Rhee, Shin Ae, Park, Kwang Sung, Kim, Yang Je, Cho, and Na Gyong, Lee
- Subjects
Lipopolysaccharides ,Mice ,Adjuvants, Immunologic ,Pseudomonas Vaccines ,Immunoglobulin G ,Pseudomonas aeruginosa ,Alum Compounds ,Animals ,Pseudomonas Infections ,Antibodies, Bacterial ,Survival Analysis - Published
- 2017
39. Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections
- Author
-
Bertrand Toussaint, Elodie Meynet, Audrey Le Gouellec, Jean Luc Lenormand, David Laurin, Boubou Camara, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), and Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)
- Subjects
0301 basic medicine ,Pseudomonas Vaccines ,medicine.drug_class ,030106 microbiology ,Antibiotics ,medicine.disease_cause ,Vaccines, Attenuated ,Cystic fibrosis ,Type three secretion system ,03 medical and health sciences ,Mice ,Immune system ,Antigen ,Immunity ,Medicine ,Animals ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Pseudomonas Infections ,Pathogen ,ComputingMilieux_MISCELLANEOUS ,Immunity, Cellular ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Pseudomonas aeruginosa ,Vaccination ,Public Health, Environmental and Occupational Health ,Pneumonia ,medicine.disease ,Antibodies, Bacterial ,3. Good health ,Immunity, Humoral ,030104 developmental biology ,Infectious Diseases ,Immunology ,Molecular Medicine ,Cytokines ,Female ,Immunization ,[SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology ,business - Abstract
Pseudomonas aeruginosa (Pa) is a significant cause of morbidity and mortality, especially in cystic fibrosis patients. Its eradication is difficult due to a wide phenotypic adaptability and an increase of its resistance to antibiotics. After the failure of several recombinant vaccines which mainly triggered humoral response, live-attenuated vaccines received attention thanks to their ability to elicit a broad immunity with both humoral- and cell-mediated responses, essential to fight this pathogen. In this study, we developed an innovative and safer live-attenuated Pa vaccine based on a Killed But Metabolically Active (KBMA) attenuation method. KBMA Pa has been further rationally designed to overexpress beneficial effectors like the type 3 secretion system apparatus. We demonstrated that KBMA Pa elicits a high and broad humoral response in mice against several antigens of particular interest such as OprF and PcrV proteins. Moreover, we assessed cytokines in the serum of immunized mice and showed that KBMA Pa elicits Th1, Th2 and especially Th17 pathways of cell-mediated immune responses. Th17 pathway involvement was also confirmed after specific stimulation of helper T cells in immunized mice. Finally, we showed that this vaccine is safe and has a protective effect in a murine acute pulmonary infectious challenge. In conclusion, KBMA Pa is a new platform with high potential for the development of a vaccine against Pa.
- Published
- 2017
40. A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients
- Author
-
Rello, Jordi, Krenn, Claus-Georg, Locker, Gottfried, Pilger, Ernst, Madl, Christian, Balica, Laura, Dugernier, Thierry, Laterre, Pierre-Francois, Spapen, Herbert, Depuydt, Pieter, Vincent, Jean-Louis, Bogár, Lajos, Szabó, Zsuzsanna, Völgyes, Barbara, Máñez, Rafael, Çakar, Nahit, Ramazanoglu, Atilla, Topeli, Arzu, Mastruzzo, Maria A., Jasovich, Abel, Remolif, Christian G., del Carmen Soria, Liliana, Andresen Hernandez, Max A., Ruiz Balart, Carolina, Krémer, Ildikó, Molnár, Zsolt, von Sonnenburg, Frank, Lyons, Arthur, Joannidis, Michael, Burgmann, Heinz, Welte, Tobias, Klingler, Anton, Hochreiter, Romana, Westritschnig, Kerstin, Universitat Autònoma de Barcelona, Supporting clinical sciences, Internal Medicine Specializations, İç Hastalıkları, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs
- Subjects
0301 basic medicine ,Male ,Soins intensifs réanimation ,Letter ,medicine.medical_treatment ,Vacunes ,Critical Care and Intensive Care Medicine ,Placebos ,Bacterial infections ,Immunocompromised host ,Vaccines ,Immunogenicity ,Vaccination ,Bacterial Infections ,Middle Aged ,Intensive Care Units ,Tolerability ,Pseudomonas aeruginosa ,Female ,Adjuvant ,Adult ,medicine.medical_specialty ,Pseudomonas Vaccines ,030106 microbiology ,Bacterial diseases ,Placebo ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Pseudomonas ,Sepsis ,medicine ,Humans ,Pseudomonas Infections ,Seroconversion ,Mortality ,Adverse effect ,Aged ,Malalties bacterianes ,business.industry ,Immunity ,medicine.disease ,vaccination ,Respiration, Artificial ,immunity ,030104 developmental biology ,Bacteremia ,Immunology ,business - Abstract
Background: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 μg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (, SCOPUS: ar.j, info:eu-repo/semantics/published
- Published
- 2017
41. Immunization with Bivalent Flagellin Protects Mice against Fatal
- Author
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Bahador, Behrouz, Farhad B, Hashemi, Mohammad Javad, Fatemi, Sara, Naghavi, Gholamreza, Irajian, Raheleh, Halabian, and Abbas Ali, Imani Fooladi
- Subjects
Immunity, Cellular ,Mice, Inbred BALB C ,Pseudomonas Vaccines ,Neutrophils ,Interleukin-17 ,Respiratory System ,Vaccination ,Immunity, Innate ,Disease Models, Animal ,Mice ,Phagocytosis ,Cell Movement ,Pseudomonas aeruginosa ,bacteria ,Animals ,Humans ,Th17 Cells ,Female ,Pseudomonas Infections ,Administration, Intranasal ,Flagellin ,Research Article - Abstract
Pseudomonas aeruginosa lung infections present a major challenge to healthcare systems worldwide because they are commonly associated with high morbidity and mortality. Here, we demonstrate the protective efficacy of type a and b flagellins (bivalent flagellin) against acute fatal pneumonia in mice. Mice immunized intranasally with a bivalent flagellin vaccine were challenged by different flagellated strains of P. aeruginosa in an acute pneumonia model. Besides the protective effect of the vaccine, we further measured the host innate and cellular immunity responses. The immunized mice in our study were protected against both strains. Remarkably, active immunization with type a or b flagellin significantly improved survival of mice against heterologous strain compared to flagellin a or b antisera. We also showed that after an intranasal challenge by P. aeruginosa strain, neutrophils are recruited to the airways of vaccinated mice, and that the bivalent flagellin vaccine was proved to be protective by the generated CD4+IL-17+ Th17 cells. In conclusion, bivalent flagellin vaccine can confer protection against different strains of P. aeruginosa in an acute pneumonia mouse model by eliciting effective cellular and humoral immune responses, including increased IL-17 production and improved opsonophagocytic killing.
- Published
- 2017
42. Vaccine development and passive immunization for Pseudomonas aeruginosa in critically ill patients: a clinical update
- Author
-
Jean Louis Vincent
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Pseudomonas Vaccines ,Critical Illness ,Population ,medicine.disease_cause ,Microbiology ,law.invention ,Sepsis ,Antibiotic resistance ,law ,medicine ,Humans ,Pseudomonas Infections ,Intensive care medicine ,education ,Clinical Trials as Topic ,Cross Infection ,education.field_of_study ,Pseudomonas aeruginosa ,business.industry ,Immunization, Passive ,Antimicrobial ,medicine.disease ,Intensive care unit ,Vaccination ,Intensive Care Units ,Immunization ,business - Abstract
ABSTRACT: Pseudomonas aeruginosa is one of the most common causes of nosocomial infection in intensive care unit patients and is independently associated with worse outcomes. Resistance of P. aeruginosa to antimicrobial agents is increasingly common and treatment of these infections is a growing challenge for intensivists. The development of methods to prevent infection, such as vaccines, is thus of considerable interest. Three agents currently show promise in this population of patients and are undergoing clinical evaluation; however, further vaccine targets are being discovered and more potential agents will likely be developed in the near future.
- Published
- 2014
43. Vaccines forPseudomonas aeruginosa: a long and winding road
- Author
-
Gregory P. Priebe and Joanna B. Goldberg
- Subjects
Pharmacology ,Pseudomonas Vaccines ,Pseudomonas aeruginosa ,Extramural ,Immunology ,Biology ,medicine.disease_cause ,Virology ,Article ,Opportunistic pathogen ,Drug Discovery ,medicine ,Humans ,Molecular Medicine ,Pseudomonas Infections - Abstract
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.
- Published
- 2014
44. Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia
- Author
-
Saeko, Hamaoka, Yoshifumi, Naito, Hideya, Katoh, Masaru, Shimizu, Mao, Kinoshita, Koichi, Akiyama, Atsushi, Kainuma, Kiyoshi, Moriyama, Ken J, Ishii, and Teiji, Sawa
- Subjects
Male ,Pore Forming Cytotoxic Proteins ,Antigens, Bacterial ,Mice, Inbred ICR ,Pseudomonas Vaccines ,Bacterial Toxins ,Freund's Adjuvant ,Aluminum Hydroxide ,Survival Analysis ,Bacterial Load ,Mice ,Treatment Outcome ,Adjuvants, Immunologic ,Oligodeoxyribonucleotides ,Pseudomonas aeruginosa ,Pneumonia, Bacterial ,Animals ,Pseudomonas Infections ,Lung - Abstract
Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.
- Published
- 2016
45. A randomized, placebo-controlled phase I study assessing the safety and immunogenicity of aPseudomonas aeruginosahybrid outer membrane protein OprF/I vaccine (IC43) in healthy volunteers
- Author
-
Bernd Jilma, Kerstin Westritschnig, Gerhard Wallner, Christa Firbas, Michael Schwameis, and Romana Hochreiter
- Subjects
Adult ,Male ,Adolescent ,Pseudomonas Vaccines ,Lipoproteins ,Recombinant Fusion Proteins ,medicine.medical_treatment ,Immunology ,Biology ,Placebo ,Injections, Intramuscular ,Immunoglobulin G ,Microbiology ,Placebos ,Young Adult ,Bacterial Proteins ,medicine ,Humans ,Immunology and Allergy ,Pharmacology ,Vaccines, Synthetic ,Immunogenicity ,Vaccination ,Antibody titer ,Middle Aged ,Antibodies, Bacterial ,Healthy Volunteers ,Tolerability ,Pseudomonas aeruginosa ,biology.protein ,Female ,Bacterial outer membrane ,Adjuvant ,Research Paper - Abstract
IC43 is a recombinant outer membrane protein-based vaccine against Pseudomonas aeruginosa (P. aeruginosa) consisting of OprF- and OprI- epitopes (Opr, outer membrane protein; OprF/I, OprF/OprI hybrid vaccine) with an N-terminal His 6 tag (Met-Ala-(His)6-OprF190-342-OprI21-83).The study aimed to confirm the optimal dose of IC43 in adults with regard to immunogenicity, safety, and tolerability after vaccination with three different dosages of IC43, compared with placebo, and to investigate a potential immune-enhancing effect of the adjuvant, aluminum hydroxide. Subjects were randomly allocated in a 1:1:1:1:1 ratio to one of five treatment groups: 50, 100, or 200 µg IC43 with adjuvant, 100 µg IC43 without adjuvant, or placebo (0.9% sodium chloride) and two intramuscular injections were given in the deltoid region 7 d apart.The primary immunogenicity analysis of OprF/I-specific IgG antibody titers on day 14 demonstrated statistically significant differences among treatment groups (P0.0001), with a significantly higher immune response detected in each IC43 treatment group compared with placebo. From day 0 to day 14, a ≥4-fold increase in OprF/I-specific immunoglobulin G (IgG) antibody titers were observed in90% of subjects in all IC43 treatment groups in the per-protocol (PP) and intention-to-treat (ITT) populations; a ≥50-fold titer increase was observed in 42.6% subjects including all IC43 treatment groups. On day 90, OprF/I-specific IgGs started to decline in all IC43 treatment groups but remained significantly higher until 6 mo compared with placebo. Assessment of functional antibody induction by opsonophagocytic assay (OPA) followed a similar pattern compared with OprF/I-specific IgG kinetics. At day 14, a ≥2-fold increase in OPA titer was observed in 54.5% subjects within all IC43 treatment groups. An increase in antibody avidity index was observed after the second vaccination. At day 14,96% of subjects in each IC43 treatment group had detectable OprF/I-specific IgG antibodies. Anti-histidine IgG antibody titers peaked on day 14 and were reduced on day 90 in all IC43 treatment groups. OprF/I-specific IgG secreted by antibody-secreting cell (ASC) was detected in all IC43 groups by B-cell ELIspot after the second vaccination and up to 6 mo. All vaccinations were safe and well tolerated up to the maximum cumulative dosage of 400 µg IC43.IC43 doses equal to or greater than 50 µg were sufficient to induce a plateau of IgG antibody responses in healthy volunteers. Higher doses, whether adjuvanted or non-adjuvanted, were not more effective.In this phase I, randomized, placebo-controlled, observer-blinded, multicenter clinical trial, 163 healthy volunteers (18-65 y) were randomly assigned to five treatment groups (1:1:1:1:1). Three groups received IC43 with adjuvant: 50 µg (n=32), 100 µg (n=33), or 200 µg (n=33). One group received IC43 100 µg without adjuvant (n=32), and one group received placebo (0.9% sodium chloride) (n=33). Each subject received two intramuscular vaccinations, separated by a 7-d interval (days 0 and 7) (Fig. 1). Humoral immune response was assessed by measurement of outer membrane protein F/I (OprF/I)-specific antibodies determined by enzyme-linked immunosorbent assay (ELISA), anti-histidine antibodies determined by ELISA, and functional antibody activity determined by opsonophagocytic assay (OPA), up to 6 mo post-vaccination. Antibody avidity was measured on days 7 and 14 from samples that had detectable vaccine antibody-specific immunoglobulin G (IgG) antibody titers. At the Austrian site only, the B-cell ELIspot assay was used to determine specific ASC responses. Safety was assessed using adverse event monitoring and clinical laboratory tests. Local and systemic tolerability was recorded in a subject diary for 7 d after each vaccination and by investigators up to 6 mo post-vaccination.
- Published
- 2013
46. RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF
- Author
-
Neil R. Hackett, Jianping Qiu, Ronald G. Crystal, Anurag Sharma, W. Z. Whu, Stefan Worgall, Anja Krause, and D. Wafadari
- Subjects
Primates ,Pseudomonas Vaccines ,Genetic Vectors ,Immunology ,Porins ,CD8-Positive T-Lymphocytes ,Adenoviridae ,Viral vector ,Microbiology ,Mice ,Immunity ,Interferon ,medicine ,Animals ,Humans ,Immunology and Allergy ,Pseudomonas Infections ,Immunity, Mucosal ,Lung ,Cells, Cultured ,biology ,Immunogenicity ,Original Articles ,Th1 Cells ,Natural killer T cell ,Mice, Inbred C57BL ,Immunoglobulin G ,CD1D ,Pseudomonas aeruginosa ,biology.protein ,Cytokines ,Female ,Antibody ,Oligopeptides ,CD8 ,medicine.drug - Abstract
Summary Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity.
- Published
- 2013
47. Herbal Sensitivity of Pseudomonas Bacteria Isolated from Cultured Tilapia with Useful Applications in Vaccine Preparation
- Author
-
Siti Fatimah Binti Sula, Mohd Salim, Mariana Nor Shamsudin, Yasser Mohamed Abdelhadi, and Khairul Afizi
- Subjects
food.ingredient ,Pseudomonas Vaccines ,General Veterinary ,Tilapia ,Pseudomonas fluorescens ,Origanum ,Biology ,biology.organism_classification ,Pseudomonas putida ,Microbiology ,Agar plate ,Minimum inhibitory concentration ,food ,Animal Science and Zoology ,Food science ,Bacteria - Abstract
The antibacterial activity of certain commercial antibiotics and common herbs was evaluated against pathogenic Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas aeruginosa isolated from Malaysian and Egyptian cultured fish, mainly tilapia. A suspension of freshly cultured isolates was prepared (with 0.5 OD) and 100 μL of this suspension was spread over the Muller’s Hinton agar plates. The antibiotic discs were inoculated on each cultured plate while the herbal extracts were soaked on Whatman filter paper (20 μL each) that have been cut into discs and later inserted on to bacteria-cultured plates to screen their sensitivity to both antibiotics and herbs. Double-fold dilution was used to determine the Minimal Inhibitory Concentration (MIC) for the effective herbs at 100, 50, 25, 12.5 and 6.25%. Results revealed high resistance of the tested bacteria against most of the screened antibiotics except Ciprofloxacin. With regard to herbal sensitivity, only Origanum vulgare showed effectiveness and inhibition zone against all isolates. The MIC ranged from 15-40% for both Egyptian and Malaysian isolates. Thus, Origanum vulgare is recommended as a feed additive for cultured fish and can also be applied for inactivated and live-attenuated Pseudomonas vaccines’ preparation.
- Published
- 2013
48. Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy
- Author
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Geoffrey Neale, Elaine Tuomanen, Peter Vogel, Paul G. Thomas, Lip Nam Loh, Akinobu Kamei, Peter J. Murray, and Geli Gao
- Subjects
0301 basic medicine ,Adoptive cell transfer ,Neutropenia ,Pseudomonas Vaccines ,Population ,Antineoplastic Agents ,Biology ,Immunophenotyping ,03 medical and health sciences ,Mice ,Immune system ,Phagocytosis ,Immunity ,Bone Marrow ,Macrophages, Alveolar ,medicine ,Macrophage ,Animals ,Pseudomonas Infections ,education ,Disease Resistance ,Mice, Knockout ,education.field_of_study ,Multidisciplinary ,Gene Expression Profiling ,Cell Cycle ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Survival Analysis ,Pneumonia ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,PNAS Plus ,Immunology ,Host-Pathogen Interactions ,Pseudomonas aeruginosa ,Bone marrow ,Biomarkers - Abstract
Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccine-induced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy-induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrow-derived monocytes, or antibodies. These vaccine-induced macrophages (ViMs) expanded after immunization, locally proliferated, and were closely related to alveolar macrophages (AMs) by surface phenotype and gene expression profiles. By contrast to AMs, numbers of ViMs were stable through chemotherapy, showed enhanced phagocytic activity, and prolonged survival of neutropenic mice from lethal P. aeruginosa pneumonia upon intratracheal adoptive transfer. Thus, induction of ViMs by tissue macrophage remodeling may become a framework for new strategies to activate immune-mediated reserves against infection in immunocompromised hosts.
- Published
- 2016
49. Protective effect of pilin protein with alum+naloxone adjuvant against acute pulmonary Pseudomonas aeruginosa infection
- Author
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Zahra Afshar, Morteza Keshavarzmehr, Abbas Zare Banadkoki, Farhad B. Hashemi, Bahador Behrouz, Neda Aleyasin, and Mohammad Javad Fatemi
- Subjects
0301 basic medicine ,Cellular immunity ,Pseudomonas Vaccines ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Bioengineering ,Booster dose ,Applied Microbiology and Biotechnology ,Pilus ,Microbiology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,medicine ,Pneumonia, Bacterial ,Animals ,Humans ,Pseudomonas Infections ,NLX ,Pharmacology ,Mice, Inbred BALB C ,General Immunology and Microbiology ,biology ,Alum ,Naloxone ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,030104 developmental biology ,chemistry ,Pilin ,Immunology ,Acute Disease ,Pseudomonas aeruginosa ,biology.protein ,Alum Compounds ,Female ,Fimbriae Proteins ,Adjuvant ,030215 immunology ,Biotechnology - Abstract
Pseudomonas aeruginosa is an important opportunistic human pathogen that causes a wide variety of severe nosocomial infections. Type IV pili of P. aeruginosa are made up of polymerized pilin that aids in bacterial adhesion, biofilm formation and twitching motility. The aim of this study was to evaluate the efficacy of alum and naloxone (alum+NLX) as an adjuvant for P. aeruginosa recombinant PilA (r-PilA) as a vaccine candidate in the improvement of humoral and cellular immunity. Primary immunization with r-PilA in combination with alum+NLX followed by two booster shots was sufficient to generate robust cellular and humoral responses, which were Th1 and Th2 type responses consisting of IgG1 and IgG2a subtypes. Analysis of the cytokine response among immunized mice showed an increased production of IL-4, INF-γ and IL-17 by splenocytes upon stimulation by r-PilA. These sera were also able to reduce bacterial load in the lung tissue of challenged mice. The reduction of systemic bacterial spread resulted in increased survival rates in challenged immunized mice. In conclusion, immunization with r-PilA combined with alum+NLX evokes cellular and humoral immune responses, which play an important role in providing protection against acute P. aeruginosa lung infection among immunized mice.
- Published
- 2016
50. Th17-stimulating Protein Vaccines Confer Protection against Pseudomonas aeruginosa Pneumonia
- Author
-
Haeyeon Hong, Martina Risech, Stephen Lory, Jin Huang, Weihui Wu, Biyan Duan, David C. Traficante, and Gregory P. Priebe
- Subjects
Pulmonary and Respiratory Medicine ,Pseudomonas Vaccines ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Vaccines, Attenuated ,Critical Care and Intensive Care Medicine ,medicine.disease_cause ,Microbiology ,Mice ,Bacterial Proteins ,Antigen ,Immunity ,Pneumonia, Bacterial ,medicine ,Animals ,Pseudomonas Infections ,Antigens, Bacterial ,biology ,Pseudomonas aeruginosa ,business.industry ,hemic and immune systems ,Articles ,Antibodies, Bacterial ,Virology ,Vaccination ,Disease Models, Animal ,Immunization ,biology.protein ,Th17 Cells ,Antibody ,business ,Adjuvant ,Spleen - Abstract
New vaccine approaches are needed for Pseudomonas aeruginosa, which continues to be a major cause of serious pulmonary infections. Although Th17 cells can protect against gram-negative pathogens at mucosal surfaces, including the lung, the bacterial proteins recognized by Th17 cells are largely unknown and could be potential new vaccine candidates.We describe a strategy to identify Th17-stimulating protein antigens of Pseudomonas aeruginosa to assess their efficacy as vaccines against pneumonia.Using a library of in vitro transcribed and translated P. aeruginosa proteins, we screened for Th17-stimulating antigens by coculturing the library proteins with splenocytes from mice immunized with a live-attenuated P. aeruginosa vaccine that is protective via Th17-based immunity. We measured antibody and Th17 responses after intranasal immunization of mice with the purified proteins mixed with the Th17 adjuvant curdlan, and we tested the protective efficacy of vaccination in a murine model of acute pneumonia.The proteins PopB, FpvA, FptA, OprL, and PilQ elicited strong IL-17 secretion in the screen, and purified versions of PopB, FpvA, and OprL stimulated high IL-17 production from immune splenocytes. Immunization with PopB, which is a highly conserved component of the type III secretion system and a known virulence factor, elicited Th17 responses and also enhanced clearance of P. aeruginosa from the lung and spleen after challenge. PopB-immunized mice were protected from lethal pneumonia in an antibody-independent, IL-17-dependent manner.Screening for Th17-stimulating protein antigens identified PopB as a novel and promising vaccine candidate for P. aeruginosa.
- Published
- 2012
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