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Biomedical subjects

A Mateczun

Publications and source records attributed to A Mateczun.

4 recordsLinked to original sources

A cationic lipid-formulated plasmid DNA vaccine confers sustained antibody-mediated protection against aerosolized anthrax spores.

DNA vaccines provide an attractive technology platform against bioterrorism agents due to their safety record in humans and ease of construction, testing, and manufacture. We have designed monovalent and bivalent anthrax plasmid DNA (pDNA) vaccines encoding genetically detoxified protective antigen (PA) and lethal factor (LF) proteins and tested their immunogenicity and ability to protect rabbits from an aerosolized inhalation spore challenge. Immune responses after two or three injections of cationic lipid-formulated PA, PA plus LF, or LF pDNAs were at least equivalent to two doses of anthrax vaccine adsorbed (AVA). High titers of anti-PA, anti-LF, and neutralizing antibody to lethal toxin (Letx) were achieved in all rabbits. Eight or nine animals in each group were challenged with 100x LD(50) of aerosolized anthrax spores 5 or 9 weeks after vaccination. An additional 10 animals vaccinated with PA pDNA were challenged >7 months postvaccination. All animals receiving PA or PA plus LF pDNA vaccines were protected. In addition, 5 of 9 animals receiving LF pDNA survived, and the time to death was significantly delayed in the others. Groups receiving three immunizations with PA or PA plus LF pDNA showed no increase in anti-PA, anti-LF, or Letx neutralizing antibody titers postchallenge, suggesting little or no spore germination. In contrast, titer increases were seen in AVA animals, and in surviving animals vaccinated with LF pDNA alone. Preclinical evaluation of this cationic lipid-formulated bivalent PA and LF vaccine is complete, and the vaccine has received U.S. Food and Drug Administration Investigational New Drug allowance.

Aerosols↗

Specificity of an immunochromatographic test for anthrax.

OBJECTIVE: To evaluate the specificity of an immunochromatographic test (ICT) for anthrax in cattle. DESIGN: A comparison of an ICT with blood smear and culture in uninfected cattle. PROCEDURE: Two hundred and forty blood samples were collected from dead cattle at two knackeries within Victoria and tested on-site with an ICT for the detection of protective antigen (PA) of Bacillus anthracis. Blood smears were prepared on-site and blood samples transported to the laboratory for aerobic and anaerobic culture. The results of the ICT were compared with blood smear and culture. Animals were regarded as not infected with B anthracis if the organism was not detected in a stained blood smear or on culture. Ten healthy yearling cattle were vaccinated with live spore anthrax vaccine and blood samples collected on days 0 to 7 and day 15 were tested in the ICT for the presence of PA. RESULTS: All blood samples from the 240 knackery cattle were ICT, smear and culture negative. All blood samples from the 10 vaccinated cattle were ICT negative. CONCLUSION: The ICT is a test with high specificity in cattle (98.5 to 100%; 95% CI) and recent vaccination of cattle does not give rise to positive reactions.

Animals↗

Protection against anthrax lethal toxin challenge by genetic immunization with a plasmid encoding the lethal factor protein.

The ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated. BALB/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids encoding either a fragment of the protective antigen (PA) or a fragment of lethal factor (LF). Plasmid pCLF4 contains the N-terminal region (amino acids [aa] 10 to 254) of Bacillus anthracis LF cloned into the pCI expression plasmid. Plasmid pCPA contains a biologically active portion (aa 175 to 764) of B. anthracis PA cloned into the pCI expression vector. One-micrometer-diameter gold particles were coated with plasmid pCLF4 or pCPA or a 1:1 mixture of both and injected into mice via gene gun (1 microg of plasmid DNA/injection) three times at 2-week intervals. Sera were collected and analyzed for antibody titer as well as antibody isotype. Significantly, titers of antibody to both PA and LF from mice immunized with the combination of pCPA and pCLF4 were four to five times greater than titers from mice immunized with either gene alone. Two weeks following the third and final plasmid DNA boost, all mice were challenged with 5 50% lethal doses of lethal toxin (PA plus LF) injected intravenously into the tail vein. All mice immunized with pCLF4, pCPA, or the combination of both survived the challenge, whereas all unimmunized mice did not survive. These results demonstrate that DNA-based immunization alone can provide protection against a lethal toxin challenge and that DNA immunization against the LF antigen alone provides complete protection.

Animals↗

Azithromycin compared with rifampin for eradication of nasopharyngeal colonization by Neisseria meningitidis.

OBJECTIVES: To evaluate the efficacy and safety of azithromycin compared with rifampin for eradication of nasopharyngeal carriage of Neisseria meningitidis METHODS: Pharyngeal swabs were obtained from 500 students attending nursing school in Cairo, Egypt, to determine the colonization rate with N. meningitidis. Colonized individuals were randomized to receive azithromycin (500 mg once) or rifampin (600 mg twice daily for four doses). Subjects were then recultured 1 and 2 weeks posttreatment to determine the effectiveness of the antibiotic therapy for eradication of meningococcal nasopharyngeal colonization. RESULTS: Individuals treated with azithromycin had a 93% eradication rate at 1 and 2 weeks posttreatment comparable with 95 and 91%, respectively, for rifampin. No significant side effects were reported by any subjects treated with either antibiotic. CONCLUSION: Azithromycin is effective in the eradication of N. meningitidis from the nasopharynx of asymptomatic colonized individuals and deserves further evaluation for use as prophylaxis against N. meningitidis.

Adolescent↗