• Biomolecules & Therapeutics
• /
• v.2 no.4
• /
• pp.322-325
• /
• 1994

To optimize the immunological efficacy of CFC-101, an outer-membrane protein vaccine purified from relatively less pathogenic 4 different Pseudomonas aeruginosa strains, we investigated to establish its dose, administration route, interval and frequency of vaccination in mice. As expected, the 4 CFC-101 producing strains were less pathogenic than the challenging organism, P. aeruginosa GN11189. CFC-101 completely protected the death caused by P. aeruginosa at above 0.05 mg/kg vaccinized by 3 times with 7-day intervals. At the optimally effective dose of 0.2 mg/kg of CFC-101, at least 3 immunizations were necessary for complete protection against P. aeruginosa-induced death. If immunized 3 times, the immunization interval could be shortened up to 2 days to acquire the best protection against P. aeruginosa. CFC-101 was effective either by intraperitoneal, subcutaneous or intramuscular but not by oral administration. The present results show that the newly developed Pseudomonas vaccine, CFC-101, is highly effective for the protection from death caused by pseudomonal infections.

• Journal of Microbiology and Biotechnology
• /
• v.7 no.2
• /
• pp.144-150
• /
• 1997

We developed a simple and efficient method to prepare a Pseudomonas vaccine of outer membrane (OM) proteins free from lipopolysaccharide (LPS). A three step purification process including extraction, ultrafiltration and ultracentrifugation effectively removed LPS from the OM protein fraction. Approximately 2 mg of the OM proteins was obtained from 1 g of wet cell. LPS contaminant in the vaccine preparation was less than 0.003% (w/w) of protein and protease activity was not detectable. To achieve a wide range of protection, OM proteins prepared from four attenuated P. aeruginosa strains were mixed in equal amounts and used as a vaccine, which elicited in rabbits a high titer of antibody reactive to all of the seven Fisher types. The antisera from the immunized rabbit had a strong reactivity to vaccine proteins larger than 25 kDa. In a burned mouse infection model, immunization with the vaccine significantly enhanced bacterial clearance in the Pseudomonas infected skin. The vaccination also provided mice an excellent protection against Pseudomonas infection (11, 16). Data on antigenicity, mutagenicity, acute, subacute toxicity and pharmacological tests confirmed the safety of the vaccine (1, 3, 10, 12, 17). These data demonstrate that this method can be applied to manufacture a bacterial vaccine of OM proteins with safety and prophylactic efficacy at a practical low cost.

• Biomolecules & Therapeutics
• /
• v.2 no.4
• /
• pp.326-330
• /
• 1994

The treatment of pseudomonal infection is a perplexed problem because of its modest susceptibility to most of the major antibiotics. A novel Pseudomonas vaccine(CFC-101) was prepared from the outer membrane protein fractions of several Pseudomonas strains. In this study, we examined CFC-101's effectiveness in both active and passive immunization models. CFC-101 in mice at 0.2 mg/kg, i.p., given three times at two-day intervals, completely prevented the death caused by Pseudomonas aeruginosa. Antibody titer, in accordance with the protective effect in this active immunization, was elevated to its peak level following three consecutive administrations of CFC-101. Thereafter, antibody titer stayed at a constantly high level. Each outer membrane protein fraction from the four CFC-101 producers, exhibited good cross-protective effects in mouse infection models against different Fisher types of P. aeruginosa. In the passive immunization model, 21~336 $\mu\textrm{g}$/kg of anti-rabbit IgG to CFC-101, when mice being infected with a challenge strain, prevented the Pseudomonhas-induced death up to 60%. Therefore, the preventive effect of CFC-101 was verified in both the active and passive immunization models.

• Biomolecules & Therapeutics
• /
• v.2 no.4
• /
• pp.331-335
• /
• 1994

As a part of the safety evaluation of Pseudomonas vaccine(CFC-101), antigenicity tests were carried out in guinea pigs and mice. In active systemic anaphylaxis(ASA) test, guinea pigs showed no sign or only moderate sign(1/5) when sensitized and challenged with up to 200 $\mu\textrm{g}$/kg. In homologous passive cutaneous anaphylaxis(PCA) test using guinea pigs, inoculation of CFC-101 alone did not produce CFC-101-specific antibody. When inoculated with 200 $\mu\textrm{g}$/kg plus adjuvant, challenge of 200 $\mu\textrm{g}$/kg produced PCA titer of 32(5/5) but challenge of 20 $\mu\textrm{g}$/kg did not produce CFC-101-specific antibody. In heterologous PCA test using mice, CFC-101-specific antibody was not detected when sensitized with CFC-101 alone. Some animals(3/12) showed positive PCA response when inoculated with 200 $\mu\textrm{g}$/kg plus alum. In passive hemagglutination (PHA) test, although no antibody was detected at 20 $\mu\textrm{g}$/kg, inoculation of 200 $\mu\textrm{g}$/kg alone or with alum produced positive response in all animals. This result has already been predicted because CFC-101 is a vaccine developed for the purpose of immunization. From the above results, it can be concluded that there is no adverse antigenic potential up to 10 times clinical dose of 200 $\mu\textrm{g}$/kg.

• Journal of Microbiology and Biotechnology
• /
• v.27 no.8
• /
• pp.1539-1548
• /
• 2017

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that commonly causes fatal infections in cystic fibrosis and burn patients as well as in patients who are hospitalized or have impaired immune systems. P. aeruginosa infections are difficult to treat owing to the high resistance of the pathogen to conventional antibiotics. Despite several efforts, no effective prophylactic vaccines against P. aeruginosa are currently available. In this study, we investigated the activity of the CIA06 adjuvant system, which is composed of alum and de-O-acylated lipooligosaccharide, on a P. aeruginosa outer membrane protein (OMP) antigen vaccine in mice. The results indicated that CIA06 significantly increased the antigen-specific IgG titers and opsonophagocytic activity of immune sera against P. aeruginosa. In addition, the antibodies induced by the CIA06-adjuvanted vaccine exhibited higher cross-reactivity with heterologous P. aeruginosa strains. Finally, mice immunized with the CIA06-adjuvanted vaccine were effectively protected from lethal P. aeruginosa challenge. Based on these data, we suggest that the CIA06 adjuvant system might be used to promote the immunogenicity and protective efficacy of the P. aeruginosa OMP vaccine.

• Pediatric Infection and Vaccine
• /
• v.13 no.2
• /
• pp.180-185
• /
• 2006

Invasive Pseudomonas infections most often occur in the immunocompromised patients and are associated with high mortality rate. Rarely this disease may develop in healthy infants and children. We report two cases of invasive Pseudomonas aeruginosa infections that were diagnosed in otherwise healthy infants. The first case was a previously healthy 5-month-old infant with ecthyma gangrenosum and septicemia. She presented with fever, swelling of left periorbital area and multiple erythronodular skin lesions. Each skin lesion formed a black eschar surrounded by an erythematous areola over time. Cultures of blood, urine and discharge from skin lesions grew P. aeruginosa. On the day of visit, she showed pancytopenia which was normalized after 10 days. The patient responded well to the management with ceftazidime and tobramycin. The other case was a previously healthy 9-month-old infant with community-acquired pneumonia. He was referred from an outside hospital with fever and cough. Chest x-ray revealed pneumonic infiltrations on both lower lungs with pleural effusion on the right side. Cultures of blood and pleural fluid grew P. aeruginosa. Chest CT performed on the ninth day demonstrated pneumatoceles, lung abscess and necrosis of lung parenchyma. He was managed with ceftazidime and amikacin for 50 days. No residual pulmonary complications were noted during the three month follow-up. Laboratory results to evaluate immunologic defects of phagocytic cells, complement components and T- and B-lymphocytes were all within normal range in both patients. It should be kept in mind that Pseudomonas can be, though uncommon, a cause of community-acquired invasive infections in the previously healthy infants.

• Parasites, Hosts and Diseases
• /
• v.58 no.2
• /
• pp.173-179
• /
• 2020

Leishmaniasis is a prevalent cause of death and animal morbidity in underdeveloped countries of endemic area. However, there is few vaccine and effective drugs. Antimicrobial peptides are involved in the innate immune response in many organisms and are being developed as novel drugs against parasitic infections. In the present study, we synthesized a 5-amino acid peptide REDLK, which mutated the C-terminus of Pseudomonas exotoxin, to identify its effect on the Leishmania tarentolae. Promastigotes were incubated with different concentration of REDLK peptide, and the viability of parasite was assessed using MTT and Trypan blue dye. Morphologic damage of Leishmania was analyzed by light and electron microscopy. Cellular apoptosis was observed using the annexin V-FITC/PI apoptosis detection kit, mitochondrial membrane potential assay kit and flow cytometry. Our results showed that Leishmania tarentolae was susceptible to REDLK in a dose-dependent manner, disrupt the surface membrane integrity and caused parasite apoptosis. In our study, we demonstrated the leishmanicidal activity of an antimicrobial peptide REDLK from Pseudomonas aeruginosa against Leishmania tarentolae in vitro and present a foundation for further research of anti-leishmanial drugs.

• Pediatric Infection and Vaccine
• /
• v.30 no.1
• /
• pp.47-54
• /
• 2023

With the widespread use of broad-spectrum antibiotics in clinical practice, the emergence of multidrug-resistant (MDR) gram-negative bacteria has become a global problem. The MDR Pseudomonas aeruginosa infection is especially difficult to treat and increases mortality in critically ill patients. Ceftolozane-tazobactam (Zerbaxa^TM) is a fifth-generation cephalosporin and beta-lactamase inhibitor that has proved to be effective for treating complicated urinary tract infections and complicated intra-abdominal infections caused by MDR P. aeruginosa. Herein, we report the first case of pediatric hematologic cancer in Korea that was successfully treated for MDR P. aeruginosa bacteremia with Ceftolozane-tazobactam.

• Pediatric Infection and Vaccine
• /
• v.9 no.1
• /
• pp.104-109
• /
• 2002

Ecthyma gangrenosum is usually seen in immunocompromised patients, particularly in those with underlying malignant disease. Ecthyma gangrenosum is rapidly progressing skin infection characterized by edema, hemorrhage, bullae and necrosis. We experienced the case of a 13-month-old male who had Ecthyma gangrenosum associated with liver abscess and renal abscess. The patient initially presented with skin lesions of multiple well defined central necrotic black colored large erythematous bullae. The multiple liver abscess with hepatomegaly and multifocal pyelonephritis with focal renal abscess revealed by abdominal ultrasonogram and computed tomogram. In the bacterial cultures of skin, urine and liver aspiration fluid, Pseudomonas aeruginosa was grown. The patient had no immune deficiency disease. We report this case with a review of related literatures.

• Pediatric Infection and Vaccine
• /
• v.25 no.1
• /
• pp.1-7
• /
• 2018

Purpose: This study aimed to determine which factors are related to perforated appendicitis. We also conducted a survey to identify the causative organism. Methods: From January 2011 to December 2014, 569 pediatric patients (322 male) younger than 19 years old who underwent an appendectomy due to acute appendicitis at Hallym University Sacred Heart Hospital were enrolled. Patients' medical records were reviewed retrospectively to determine their clinical manifestations, laboratory and imaging results, and pathogens. Results: About 127 patients (22%) had perforated appendicitis. The rate of perforated appendicitis in preschool, late childhood, and adolescent ages were 50%, 27%, and 16.8%, respectively. The risk factors of perforation were high C-reactive protein levels and the presence of appendiceal fecalith (P<0.001). Of the 24 samples of peritoneal fluid and periappendiceal pus that were collected intraoperatively, 16 were culture positive. The most common pathogen was Escherichia coli (n=10), and others were Pseudomonas aeruginosa, Streptococcus spp., and Staphylococcus spp. Conclusions: The perforation rate of appendicitis among patients younger than 5 years old was 50%, and this decreased in proportion with age. Clinicians should be aware of the possibility of perforation when patients with appendicitis have high C-reactive protein levels or the presence of appendiceal fecalith on imaging.