Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens

Song, B.M.,Kang, H.M.,Lee, E.K.,Jung, S.C.,Kim, M.C.,Lee, Y.N.,Kang, S.M.,Lee, Y.J. Butterworths ; Elsevier Science Ltd 2016 Vaccine Vol.34 No.5

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry.

닭의 동품종내 계통간 잡종강세 이용시험

박상문,김동곤,송기덕,오봉국 한국축산학회 1965 한국축산학회지 Vol.7 No.1

To induce hybrid vigor by the reciprocal crossing with SWL (Sung Whan Line), MWL (Minnesota Line), AWL (Dembro Line) and BWL (Derby Line) of single comb white leghorn, 1,330 hens were divided into 16 blacks (Diallal cross with four Line) and fed under condition of N.R.C. feeding standard. In this experiment, hatchability, fertility, mortality, body weight, days required on up to first egg laying date, egg weight, egg quality, winter pauses, intensity, feed utilization, number of eggs layed during the testing period of days and brooding were investigated. Cross breeds showed a little higher fertility and hatchability but there were no significance when their parents had high hatchability. Cross breeds M♀×A♂, M♀×E♂ and A♀×S♂ showed more than ½ decrease in mortality, however cross bred hen showed 2.27% more decrease in mortality than purebreeds. Cross breeds of 6 blocks among 16 blocks at 6 weeks showed significant (P$lt;0.01) difference in body weight. Heaviest cross breed among all blocks were S♀×A♂ and A♀×S♂. Generally adult cross breeds showed heaviest body weight; especially in S♀×A♂ and A♀×S♂ cross breeds showed heaviest body weight among them. Dates requiring on up to first egg laying (50% laying date in the blocks) were showen at cross breeds. Cross breeds shorten 16.42 days than purebreeds and A♀×M♂ was showed shortest clay (171.0 days) in all cross breeds. ♀M×A♂ (175.0 days) and M♀×B♂ (175.0 days) were excellent. Cross breed showed increased egg weight as follows : A♀×S♂ 56.0 g, B♀×M♂ 56.62 g B♀×A♂ 57.40 g and there was significant (P$lt;0.05) difference in egg weight between pure breed and cross breed (M♀×S♂ and B♀×A♂), However, their egg weight was same one as standard (56.0 g) Generally productive block showed light egg weight, because egg weight are related to egg production, Those eggs didn't show any progress in thickness, meat and blood spot. Winter pauses became more short and intensity was more higher than purebreeds. They produced more eggs during winter than purebreeds. Feed utilization was very high in cross breeds. than in purebreeds. The number of egg at 500 days testing period (Hen house) was M♀×B♂ : 201,08, S♀×B♂ : 200.73, B♀×S♂ : 200.21, M♀×S♂ : 197.28 and M♀×A♂ : 191.69 and number of egg per hen in the block was from 230 to 256 in a year. SWL and BWL cross was very excellent in any condition. Generally, we could say that the number of egg was increased by crossing and it showed at 1% level of significance, but cross breeds increased broodiness about 0.56% than did in pure breeds.

Gemcitabine–oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed

Lee, J-L,Ahn, J-H,Choi, M K,Kim, Y,Hong, S-W,Lee, K-H,Jeong, I-G,Song, C,Hong, B-S,Hong, J H,Ahn, H Nature Publishing Group 2014 The British journal of cancer Vol.110 No.10

<P><B>Background:</B></P><P>There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC).</P><P><B>Methods:</B></P><P>The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m<SUP>−2</SUP> and oxaliplatin 100 mg m<SUP>−2</SUP> intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate.</P><P><B>Results:</B></P><P>The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m<SUP>−2</SUP>. A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38–72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4–7.2) and the median overall survival was 17.6 months (95% CI, 12.6–22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%).</P><P><B>Conclusions:</B></P><P>The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).</P>

Early Regulation of Viral Infection Reduces Inflammation and Rescues Mx-positive Mice from Lethal avian Influenza Infection

Song, M.S.,Cho, Y.H.,Park, S.J.,Pascua, P.N.Q.,Baek, Y.H.,Kwon, H.I.,Lee, O.J.,Kong, B.W.,Kim, H.,Shin, E.C.,Kim, C.J.,Choi, Y.K. American Association of Pathologists and Bacteriol 2013 The American journal of pathology Vol.182 No.4

Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1<SUP>-/-</SUP>) and congenic Mx1-expressing (B6-Mx1<SUP>+/+</SUP>) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1<SUP>+/+</SUP> mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1<SUP>-/-</SUP> mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1<SUP>-/-</SUP> mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1<SUP>-/-</SUP> mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1<SUP>-/-</SUP> mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Kim, E-K,Seo, H-S,Chae, M-J,Jeon, I-S,Song, B-Y,Park, Y-J,Ahn, H M,Yun, C-O,Kang, C-Y Macmillan Publishers Limited 2014 Gene therapy Vol.21 No.1

For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives

Song, J.M.,Park, K.D.,Lee, K.H.,Byun, Y.H.,Park, J.H.,Kim, S.H.,Kim, J.H.,Seong, B.L. Elsevier/North-Holland 2007 ANTIVIRAL RESEARCH Vol.76 No.2

Catechin derivatives with different alkyl chain length and aromatic ring substitutions at the 3-hydroxyl group were synthesized from epigallocatechin (EGC) and (+)-catechin (C) and their anti-influenza viral activity were evaluated in vitro and in ovo. Pronounced antiviral activity was observed for derivatives carrying moderate chain length (7-9 carbons) as compared to those with aromatic rings, whereas the 5'-hydroxyl group of the trihydroxy benzyl moiety did not significantly contribute to antiviral activity. The derivatives exerted inhibitory effects for all six influenza subtypes tested including three major types of currently circulating human influenza viruses (A/H1N1, A/H3N2 and B type), H2N2 and H9N2 avian influenza virus. The compounds strongly inhibited adsorption of the viruses on red blood cell (RBC). They also restricted the growth of avian influenza virus in ovo with minimum inhibition concentration (MIC) of 5-10μM far exceeding the neuraminidase (NA) inhibitor oseltamivir or M2 proton channel inhibitor amantadine. The antiviral activity appears to be mediated by interaction with hemagglutinin (HA)/viral membrane rendering HA less fusogenic at the initial stage of infection. The broad spectrum activity against various subtypes of influenza viruses may complement the limitations of current antivirals and contribute for managing potentially emerging influenza pandemic. The structure-activity data of catechin derivatives may usefully guideline future research endeavors for applying green tea catechins as alternative anti-viral agents.

Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models

Song, J.H.,Kim, J.Y.,Piao, C.,Lee, S.,Kim, B.,Song, S.J.,Choi, J.S.,Lee, M. Elsevier Science Publishers 2016 Journal of controlled release Vol.234 No.-

<P>In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGBIA is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALls. HMGBIA has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGBIA, the HMGBIA/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGBIA and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113 nm and 25 mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A,ffieparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, more effectively than HMGBIA or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1Affieparin complex might be useful to treat ALI. (C) 2016 Elsevier B.V. All rights reserved.</P>

Cloning of the Structural Gene for Hepatitis B Virus Surface Antigen into a Yeast Vector

김경태,송기방,최영철,이상기,한문희,Kim, K.T.,Song, K.B.,Choi, Y.C.,Rhee, S.K.,Han, M.H. 생화학분자생물학회 1985 한국생화학회지 Vol.18 No.2

B형간염 virus의 표면항원(HBsAg) 유전자를 alcohol dehydrogenase (ADCI) 유전자의 promoter를 갖고 있으며 Escherichia coli와 효모인 Saccharomyces cerevisiae에서 자기복제할 수 있는 shuttle vector pAAR 6에 cloning하였다. 표면항원 유전자가 cloning된 재조합 plasmid를 S. cerevisiae SHY 3, YNN 27, D 13, ATCC 38517, ATCC 42677 등의 균주에 형질전환시켜 배양한 후 이들 균주로부터 virus의 표면항원이 생산됨을 방사능 면역측정법으로 확인하였다. 사용한 균주중 YNN 27주에서 가장 많은 표면항원 단백질이 생산되었고 이를 sucrose gradient centrifugation, CsCl density gradient 및 전자현미경으로 조사한 결과 간염환자의 혈청으로부터 분리한 22 nm 크기의 표면항원입자와 형태와 크기면에서 유사한 물질임이 확인되었다. The structural gene of hepatitis B virus surface antigen (HBsAg) was cloned into a shuttle vector pAAR 6 which is capable of autonomous replication and selection in both of the yeast Saccharomyces cerevisiae and Escherichia coli. This expression vector employs the 5'-flanking region of ADC I gene as a promoter in order for transcribing viral surface antigen coding sequences. After transformation of the recombinant plasmid into yeast strains such as SHY 3, YNN 27, D 13, ATCC 38517 and ATCC 42677, the expression of HBsAg gene in the host cells was evident. The protein synthesized in yeast cells was found to be similar in size, density and shape to the 22 nm particles isolated from the plasma of human hepatitis carriers.

Partial conductivities of mixed conducting BaCe_0.65Zr_0.2Y_0.15O_3–δ

Lim, D.-K.,Park, C.-J.,Choi, M.-B.,Park, C.-N.,Song, S.-J. Elsevier 2010 International journal of hydrogen energy Vol.35 No.19

<P><B>Abstract</B></P><P>The electrical properties of BaCe<SUB>0.65</SUB>Zr<SUB>0.2</SUB>Y<SUB>0.15</SUB>O<SUB>3–δ</SUB> (BCZY) were studied as a function of both oxygen partial pressure and water vapor partial pressure in the temperature range of 500–800 °C, and the partial conductivities of protons, holes, and oxygen vacancies were calculated from the defect model. P-type conduction was dominant in an oxidative atmosphere. In a wet atmosphere, BCZY was a mixed conductor of protons, holes, and oxygen ions. A conduction transition from protons to holes and/or oxygen ions was found with increasing temperature. The calculated activation energy of oxygen ion transport was 0.71 eV. The standard solution enthalpy for water dissolution was best fitted with a slope of −120.19 kJ/mol, which is somewhat smaller in absolute terms than that of BaCe<SUB>0.9</SUB>Y<SUB>0.1</SUB>O<SUB>3–δ</SUB> and of BaCe<SUB>0.8</SUB>Y<SUB>0.2</SUB>O<SUB>3–δ</SUB>. This result also agrees well with the literature reports that the Ba, rather than Sr, occupation of A-site and the Ce, rather than Zr, occupation of B-site in perovskite proton conductors induce more negative hydration enthalpies due to the increasing basicity of the corresponding oxides.</P>