Parenteral application of a Pseudomonas aeruginosa flagella vaccine elicits specific anti-flagella antibodies in the airways of healthy individuals.

Döring, Gerd; Pfeiffer, Carola; Weber, Ursula; Mohr-Pennert, Anita; Dorner, Friedrich

doi:10.1164/ajrccm.151.4.7697276

Cited by 28 publications

(22 citation statements)

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“…Our previous studies of this acute pneumonia model indicated that death from pneumonia was highly correlated with systemic spread of bacteria (1). It therefore follows that survival of the PAO1⌬aroA-immunized mice is due to prevention of the dis- (8,23,31), on outer membrane proteins (27,32,40) and, more recently, on the PcrV antigen component of the type III secretion system (15,24,55,57). We note that, in these later studies, protection against lethal pneumonia has only been demonstrated with P. aeruginosa strain PA103, a highly virulent, ExoU ϩ strain that can be given to mice at a relatively low inoculum to generate lethality.…”

Section: Discussionmentioning

confidence: 84%

Protection against FatalPseudomonas aeruginosaPneumonia in Mice after Nasal Immunization with a Live, AttenuatedaroADeletion Mutant

et al. 2003

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Studies of immunity to Pseudomonas aeruginosa have indicated that a variety of potential immunogens can elicit protection in animal models, utilizing both antibody-and cell-mediated immune effectors for protection. To attempt to optimize delivery of multiple protective antigens and elicit a broad range of immune effectors, we produced an aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1, designated PAO1⌬aroA. Previously, we reported that this strain elicits high levels of opsonic antibody directed against many serogroup O2/O5 strains after nasal immunization of mice and rabbits. Here, we assessed the protective efficacy of immunization with PAO1⌬aroA against acute fatal pneumonia in mice. After active immunization, high levels of protection were achieved against an ExoU-expressing cytotoxic variant of the parental strain PAO1 at doses up to 1,000-fold greater than the 50% lethal dose. Significant protection against PAO1 and two of four other serogroup O2/O5 strains was also found, but there was no protection against serogroupheterologous strains. The serogroup O2/O5 strains not protected against were killed in opsonophagocytic assays as efficiently as the strains with which protection was seen, indicating a lack of correlation of protection and opsonic killing within the serogroup. In passive immunization experiments using challenge with wild-type PAO1 or other noncytotoxic members of the O2/O5 serogroup, there was no protection despite the presence of high levels of opsonic antibody in the mouse sera. However, passive immunization did prevent mortality from pneumonia due to the cytotoxic PAO1 variant at low-challenge doses. These data suggest that a combination of humoral and cellular immunity is required for protection against P. aeruginosa lung infections, that such immunity can be elicited by using aroA deletion mutants, and that a multivalent P. aeruginosa vaccine composed of aroA deletion mutants of multiple serogroups holds significant promise.Nosocomial infections due to the opportunistic pathogen Pseudomonas aeruginosa are a significant clinical problem (10,14,53). These infections, as well as community-acquired corneal infections in wearers of extended-use contact lenses (47,56), are due to lipopolysaccharide (LPS)-smooth strains of P. aeruginosa, which are distinct from the LPS-rough, mucoid strains found in patients with advanced cystic fibrosis (18). It should be noted, however, that the initial colonizing strains in cystic fibrosis patients are typically LPS smooth (4). The difficulties in treating P. aeruginosa infections are particularly noteworthy. These difficulties stem not only from host factors, such as immunocompromise or the presence of foreign material, but also from bacterial factors such as biofilm formation and intrinsic antibiotic resistance, which have shown a disturbingly rising frequency (16). The intrinsic antibiotic resistance of P. aeruginosa is largely due to the presence of multiple drug efflux pumps (49) and the low permeability of the outer membrane (17)....

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Section: Discussionmentioning

confidence: 84%

Protection against FatalPseudomonas aeruginosaPneumonia in Mice after Nasal Immunization with a Live, AttenuatedaroADeletion Mutant

et al. 2003

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“…A monovalent P. aeruginosa lagella vaccine was safe and immunogenic in healthy human adults by intramuscular immunization and showed high and long-lasting serum antibody (IgG and IgA) titers against lagella positive P. aeruginosa [130].…”

Section: Antibody and Vaccine Development Against Lagellins And Pilinsmentioning

confidence: 99%

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

Zhang¹,

Su²,

Wu³

2017

Physiology and Pathology of Immunology

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Multidrug-resistant bacteria (MDR) are increasing rapidly and posing a global threat to mankind. Alternative strategies other than antibiotics have to be explored urgently. In this chapter, we review the current status of nonantibiotics strategies including antibodybased therapy and vaccine development for targeting Gram-positive strains (methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium) and MDR Gram-negative strains (Acinetobacter baumannii and Pseudomonas aeruginosa). Biologicsbased clinical progress against these bacterial infections is updated.

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“…78,79 Intramuscular administration of a monovalent P. aeruginosa flagella vaccine was well tolerated in healthy volunteers and elicited high and long-lasting systemic and lung antibody titers. 80 In a double-blind, placebocontrolled, randomized, multicenter phase III trial on 483 CF patients without P. aeruginosa colonization 4 intramuscular injections of a bivalent P. aeruginosa flagella vaccine were given Elastase and alkaline proteases interfere with the host immune system by cleaving immunoglobulins, 112,113 inhibiting cytokines, 114,115 and interfering with the immune cell functions. [116][117][118] Immunization with elastase and alkaline protease toxoids were effective in P. aeruginosa infection models of hemorrhagic pneumonia in minks, 119 corneal ulcers 120 and burns in mice.…”

Section: Flagellamentioning

confidence: 99%

Recent developments for Pseudomonas vaccines

2011

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Parenteral application of a Pseudomonas aeruginosa flagella vaccine elicits specific anti-flagella antibodies in the airways of healthy individuals.

Cited by 28 publications

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Protection against FatalPseudomonas aeruginosaPneumonia in Mice after Nasal Immunization with a Live, AttenuatedaroADeletion Mutant

Protection against FatalPseudomonas aeruginosaPneumonia in Mice after Nasal Immunization with a Live, AttenuatedaroADeletion Mutant

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

Recent developments for Pseudomonas vaccines

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