Osong Public Health and Research Perspectives

Brief Report

Ebola Hemorrhagic Fever and the Current State of Vaccine Development: Joo Eun Hong, Kee-Jong Hong, Woo Young Choi, Won-Ja Lee, Yeon Hwa Choi, Chung-Hyeon Jeong, Kwang-il Cho; Osong Public Health Res Perspect. 2014;5(6):378-382. Published online December 31, 2014; DOI: https://doi.org/10.1016/j.phrp.2014.09.006

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Current Ebola virus outbreak in West Africa already reached the total number of 1,323 including 729 deaths by July 31st. the fatality is around 55% in the southeastern area of Guinea, Sierra Leone, Liberia, and Nigeria. The number of patients with Ebola Hemorrhagic Fever (EHF) was continuously increasing even though the any effective therapeutics or vaccines has not been developed yet. The Ebola virus in Guinea showed 98% homology with Zaire Ebola Virus.Study of the pathogenesis of Ebola virus infection and assess of the various candidates of vaccine have been tried for a long time, especially in United States and some European countries. Even though the attenuated live vaccine and DNA vaccine containing Ebola viral genes were tested and showed efficacy in chimpanzees, those candidates still need clinical tests requiring much longer time than the preclinical development to be approved for the practical treatment.It can be expected to eradicate Ebola virus by a safe and efficient vaccine development similar to the case of smallpox virus which was extinguished from the world by the variola vaccine.

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Articles

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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Abstract PDF

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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A therapeutic human antibody against the domain 4 of the Bacillus anthracis protective antigen shows protective efficacy in a mouse model
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Expression and refolding of the protective antigen of Bacillus anthracis: A model for high-throughput screening of antigenic recombinant protein refolding
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In vivo Noninvasive Small Animal Molecular Imaging: Hyewon Youn, Kee-Jong Hong; Osong Public Health Res Perspect. 2012;3(1):48-59. Published online December 31, 2011; DOI: https://doi.org/10.1016/j.phrp.2012.02.002

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Abstract PDF

The remarkable efforts that are made on molecular imaging technologies demonstrate its potential importance and range of applications. The generation of disease-specific animal models, and the developments of target-specific probes and genetically encoded reporters are another important component. Continued improvements in the instrumentation, the identification of novel targets and genes, and the availability of improved imaging probes should be made. Multimodal imaging probes should provide easier transitions between laboratory studies, including small animal studies and clinical applications. Here, we reviewed basic strategies of noninvasive in vivo imaging methods in small animals to introducing the concept of molecular imaging.

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Original Article

Ingenol Protects Human T Cells From HIV-1 Infection: Kee-Jong Hong, Hak Sung Lee, Yeong-shik Kim, Sung Soon Kim; Osong Public Health Res Perspect. 2011;2(2):109-114. Published online June 30, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.07.001

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Abstract PDF

Objectives
Many natural compounds have been investigated as drug candidates to prevent human immunodeficiency virus (HIV) with low cytotoxicity. We tested whether ingenol from Euphorbia ingens exerts anti-HIV effects in human T cell lines.
Methods
and Results Ingenol effectively maintained high cell viability (CD₅₀, >1 mM) in H9 and MT4 T cells. The efficacy of ingenol to inhibit HIV-1 infection was dose dependent. ED₅₀ for 100 and 200 TCID₅₀ of HIV-1 was 5.06 and 16.87 μM, respectively. Gag p24 antigen production in ingenol-treated MT4 cells was reduced by 24.5% on day 6 post-infection. While p24 antigen was reduced in ingenol-treated cells, levels of cytokines such as TNF-α and IL-6 and chemokines such as RANTES and MCP-1 were increased. dUTP level related to late apoptotic events was increased on day 2 post-infection of HIV by ingenol treatment, whereas expression of annexin V was unchanged. Reduced levels of iNOS and ZAP-70 after HIV infection were recovered by ingenol treatment.
Conclusion
Ingenol helps T cells to survive longer against viremia after HIV-1 infection, without exerting cytotoxic effects. Ingenol can be considered a safe and efficacious candidate for immune-boosting therapy for AIDS patients.

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