Osong Public Health and Research Perspectives

Article

Serological Correlate of Protection in Guinea Pigs for a Recombinant Protective Antigen Anthrax Vaccine Produced from Bacillus brevis: Jeong-Hoon Chun, On-Jee Choi, Min-Hee Cho, Kee-Jong Hong, Won Keun Seong, Hee-Bok Oh, Gi-Eun Rhie; Osong Public Health Res Perspect. 2012;3(3):170-176. Published online June 30, 2012; DOI: https://doi.org/10.1016/j.phrp.2012.07.006

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Objective Recombinant protective antigen (rPA) is the active pharmaceutical ingredient of a second generation anthrax vaccine undergoing clinical trials both in Korea and the USA. By using the rPA produced from Bacillus brevis pNU212 expression system, correlations of serological immune response to anthrax protection efficacy were analyzed in a guinea pig model.
Methods
Serological responses of rPA anthrax vaccine were investigated in guinea pigs that were given single or two injections (interval of 4 weeks) of various amounts of rPA combined with aluminumhydroxide adjuvant. Guinea pigs were subsequently challenged by the intramuscular injection with 30 half-lethal doses (30LD₅₀) of virulent Bacillus anthracis spores. Serumantibody titerswere determined by anti-PA IgGELISA and the ability of antibodies to neutralize the cytotoxicity of lethal toxin on J774A.1 cell was measured through the toxin neutralizing antibody (TNA) assay.
Results
To examine correlations between survival rate and antibody titers, correlation between neutralizing antibody titers and the extent of protection was determined. Toxin neutralization titers of at least 1176 were sufficient to confer protection against a dose of 30LD₅₀ of virulent anthrax spores of the H9401 strain. Such consistency in the correlation was not observed from those antibody titers determined by ELISA.
Conclusion
Neutralizing-antibody titers can be used as a surrogate marker.

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Original Articles

Pathogenesis and Chronologic Localization of the Human Influenza A (H1N1) Virus in Cotton Rats: Donghyok Kwon, Kyeongcheol Shin, Jin-Young Shin, Joo-Yeon Lee, Yooncheol Ha, Nam-Joo Lee, Hee-Bok Oh, Chanhee Chae, Chun Kang; Osong Public Health Res Perspect. 2011;2(1):15-22. Published online June 30, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.04.005

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Abstract PDF

Objectives
We aimed to evaluate the pathogenesis and chronologic localization of human influenza A (H1N1) virus in experimentally infected cotton rats.
Methods
The animals were intranasally inoculated with 10⁷ plaque-forming units of A/Solomon Islands/3/2006 (H1N1) influenza virus and evaluated for pathogenicity for a period of 28 days. Virus replication kinetics and pathological properties were assessed chronologically. Acute antiviral responses were evaluated by mean of real-time polymerase chain reaction.
Results
Cotton rats infected with A/Solomon Islands/3/2006 virus lost weight until 6 days post-inoculation (DPI) and showed decreased activity until 3 DPI. At necropsy, focal areas of redness and consolidation of lungs were evident at 1, 2, and 3 DPI. Lung histopathology showed moderate to severe interstitial pneumonia, alveolitis and bronchiolitis. Influenza A specific viral protein was detected in bronchiolar epithelial cells, alveolar septa and pneumocytes. Influenza viruses were recovered from the lungs during the early period of infection and the titer peaked at 1 DPI. Viral proteins were detected from 4 hours to 6 hours DPI. These trends correlate with the up-regulation of mRNA expression of the IFN-α, Mx1, and Mx2 genes that play critical roles in the anti-influenza response at the early stage of infection.
Conclusion
Our results provide evidence that supports the use of cotton rats for the study of influenza virus pathogenesis and the immune response.

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Distribution of Virulence Genes and Their Association of Serotypes in Pathogenic Escherichia coli Isolates From Diarrheal Patients in Korea: Seung-Hak Cho, Kyung-Hwan Oh, Seong-Han Kim, Hee-Bok Oh, Mi-Sun Park; Osong Public Health Res Perspect. 2010;1(1):29-35. Published online December 31, 2010; DOI: https://doi.org/10.1016/j.phrp.2010.12.008

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Abstract PDF

Objectives
To characterise the genetic and serological diversity of pathogenic Escherichia coli, we tested 111 E coli strains isolated from diarrhoeal patients in Korea between 2003 and 2006.
Methods
The isolates were tested through polymerase chain reaction (PCR) and slide agglutination method for the detection of virulence genes and serotypes, respectively. To compare the expression of Shiga toxin (stx)-1 and stx2 genes, real-time quantitative reverse-transcriptase PCR and rapid exprssion assay, reversed-passive latex agglutination, were performed.
Results
Forty-nine Shiga toxin-producing E coli (STEC) strains and 62 non-STEC strains, including 20 enteropathogenic E coli, 20 enterotoxigenic E coli, 20 enteroaggregative E coli, and 2 enteroinvasive E coli were randomly chosen from the strains isolated from diarrhoeal patients in Korea between 2003 and 2006. PCR analysis indicated that locus of enterocyte effacement pathogenicity island, that is, eaeA, espADB, and tir genes were present in STEC, enteropathogenic E coli, and enteroinvasive E coli. Quorum sensing-related gene luxS was detected in most of pathogenic E coli strains. Major serotypes of the STEC strains were O157 (26%) and O26 (20%), whereas the non-STEC strains possessed various serotypes. Especially, all the strains with serotype O157 carried stx2 and the tested virulence factors. Of the STEC strains, the data of real-time quantitative reverse-transcriptase PCR and reversed-passive latex agglutination tests showed that messenger RNA- and protein expression of stx2 gene were higher than those of stx1 gene.
Conclusion
Our results provide the epidemiological information regarding the trend of STEC and non-STEC infections in the general population and show the fundamental data in association of serotypes with virulence genes in diarrhoeagenic E coli strains from Korea.

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