OprF/I-vaccinated sera inhibit binding of human interferon-gamma to Pseudomonas aeruginosa.

The recombinant outer membrane protein OprF/I has been demonstrated in previous studies to protect against Pseudomonas aeruginosa infection through a mechanism of enhanced antibody-mediated opsonophagocytosis. Recent evidence indicates that P. aeruginosa enhances its virulence phenotype as a consequence of binding to human IFN-gamma through an outer membrane protein, OprF.

Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: a clinical trial of immunogenicity in lower airways of human volunteers.

Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies. We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination.

Immune responses in the airways by nasal vaccination with systemic boosting against Pseudomonas aeruginosa in chronic lung disease.

Rationale: Pneumonia caused by Pseudomonas (P.) aeruginosa is a leading cause of morbidity and mortality in patients with chronic lung diseases. Systemic vaccination in patients with cystic fibrosis has been only successful in part.

Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study.

Background: Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial.

Methods: N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6) or a nasal booster vaccination (n = 6).

A three-step purification method of large quantities of human recombinant alpha endothelial cellular growth factor for clinical use.

The endothelial cellular growth factor alpha-ECGF is a candidate drug for the induction of therapeutic neoangiogenesis. Its use in extensive experimental and clinical trials is hampered by the fact that currently published purification procedures allow only small yields, and the absence of pyrogenic impurities is not demonstrated. The rh alpha-ECGF was expressed in E.

Enhanced immunogenicity in the murine airway mucosa with an attenuated Salmonella live vaccine expressing OprF-OprI from Pseudomonas aeruginosa.

We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model. Strains with in vivo inducible protein expression with the PpacC promoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone.

Humoral immune response against proteophosphoglycan surface antigens of Entamoeba histolytica elicited by immunization with synthetic mimotope peptides.

The protozoan parasite Entamoeba histolytica, which is responsible for intestinal amebiasis and amebic liver abscess, is causing significant morbidity and mortality worldwide. Proteophosphoglycans (PPGs, also known as lipophosphoglycans, LPGs, or lipopeptidophosphoglycans, LPPGs) are major surface components of E. histolytica.

Mucosal vaccination with a recombinant OprF-I vaccine of Pseudomonas aeruginosa in healthy volunteers: comparison of a systemic vs. a mucosal booster schedule.

We compared the immunogenicity of two vaccination schedules with either a systemic or a mucosal booster, both following a mucosal primary vaccination with a recombinant outer membrane fusion protein of Pseudomonas aeruginosa (OprF-I) in 12 healthy volunteers. The systemic booster induced higher levels of OprF-I-specific serum antibodies of IgG isotype, with a mean+/-S.E.

Clinical study to assess the immunogenicity and safety of a recombinant Pseudomonas aeruginosa OprF-OprI vaccine in burn patients.

In a recent clinical trial we evaluated the safety and immunogenicity of a recombinant OprF-OprI vaccine consisting of the mature outer membrane protein I (OprI) and amino acids 190-342 of OprF of Pseudomonas aeruginosa in burn patients and compared the elicited antibodies with antibodies against tetanus as response to a simultaneous immunization given on the day of admission. Safety and immunogenicity of the vaccine had been tested before in healthy human volunteers as published in 1999. In this first clinical trial we immunized eight burn patients suffering from second or third degree burns involving between 35% and 55% of the body surface three times with 100 microg of the OprF-OprI vaccine.

Effect of in situ expression of human interleukin-6 on antibody responses against Salmonella typhimurium antigens.

In an attempt to trigger increased mucosal secretory immune responses against bacterial surface antigens, we constructed an optimized human interleukin (hIL)-6-secreting Salmonella typhimurium strain (X4064(pCH1A+pYL3E)), utilizing the hemolysin (Hly) exporter for secretory delivery of a functional hIL-6-hemolysin fusion protein (hIL-6-HlyA(s)). Through stable introduction of a second hIL-6-HlyA(s) expression plasmid (pYL3E) in the previously described X4064(pCH1A) strain, hIL-6-HlyA(s) secretion efficiencies were increased by at least 10-fold. As pCH1A in the parental strain, pYL3E was stable in vitro in the absence of antibiotic selection and in vivo neither did plasmids interfere in their stabilities.

Secretory delivery of recombinant proteins in attenuated Salmonella strains: potential and limitations of Type I protein transporters.

Live attenuated Salmonella strains have been extensively explored as oral delivery systems for recombinant vaccine antigens and effector proteins with immunoadjuvant and immunomodulatory potential. The feasibility of this approach was demonstrated in human vaccination trials for various antigens. However, immunization efficiencies with live vaccines are generally significantly lower compared to those monitored in parenteral immunizations with the same vaccine antigen.

Comparison of protein with DNA therapy for chronic myocardial ischemia using fibroblast growth factor-2.

Objective: Treatment of coronary disease by growth factors has become an increasingly used strategy for otherwise untreatable patients and is subject to a number of clinical studies. The aim is to stimulate the development of a sufficient collateral circulation and hereby to rescue cardiac function. The objective of our study was to compare the effectiveness of fibroblast growth factor-2 (FGF-2) as protein and as naked plasmid DNA in a porcine model of chronic myocardial ischemia.

Cloning and hemolysin-mediated secretory expression of a codon-optimized synthetic human interleukin-6 gene in Escherichia coli.

Previously, we constructed human interleukin-6 (hIL-6)-secreting Escherichia coli and Salmonella typhimurium strains by fusion of the hIL-6 cDNA to the HlyA(s) secretional signal, utilizing the hemolysin export apparatus for extracellular delivery of a bioactive hIL-6-hemolysin (hIL-6-HlyA(s)) fusion protein. Molecular analysis of the secretion process revealed that low secretion levels were due to inefficient gene expression. To adapt the codon usage in hIL-6 cDNA to the E.

Antigenicity and immunogenicity of phage library-selected peptide mimics of the major surface proteophosphoglycan antigens of Entamoeba histolytica.

Entamoeba histolytica is the protozoan parasite responsible for intestinal amoebiasis and amoebic liver abscess, which cause significant morbidity and mortality in many countries of the world. Proteophosphoglycans (PPGs, also known as lipophosphoglycans, LPGs, or lipopeptidophosphoglycans, LPPGs) represent dominant surface components of E. histolytica.

Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas aeruginosa.

The outer membrane protein F gene (oprF) of Pseudomonas aeruginosa was recently shown by us to protect mice from P. aeruginosa chronic pulmonary infection when used as a DNA vaccine administered by three biolistic (gene gun) intradermal inoculations given at 2-week intervals. In the present study, we used two different strategies to improve the protective efficacy of the DNA vaccine.