Department of Cell Research and Immunology, the George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel
Background: HIV-1 infection of target cells is mediated via the binding of the viral envelope protein, gp120, to the cell surface receptor CD4. This interaction leads to conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for the subsequent recognition of the co-receptor required for viral entry. The CD4-bound state of gp120 has been considered as a potential immunogen for HIV-1 vaccine development.
In this research we propose an alternative means to induce gp120 into the CD4i conformation.
Results: Combinatorial phage display peptide libraries were screened against HIV-1 gp120 and short (14aa) peptides were selected that bind the viral envelope and allosterically induce the CD4i conformation. The lead peptide was subsequently systematically optimized for higher affinity as well as more efficient inductive activity. The peptide: gp120 complex was scrutinized with a panel of neutralizing anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide binding does not interfere with or obscure the CD4 binding site.
Conclusions: Two surfaces of gp120 are considered targets for the development of cross neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By implementing novel peptides that allosterically induce the CD4i epitopes we have generated a viral envelope that presents both of these surfaces simultaneously.
Biography:
Anna Roitburd-Berman completed her B.Sc. in Biology at the George S. Wise Faculty of Life Sciences, Tel Aviv University in 2005 and proceeded with her studies in the Direct Ph.D. Program at the Department of Cell Research and Immunology, Tel Aviv University. Over the past 10 years she has been studying the interaction between the HIV-1 envelope glycoprotein, gp120, and its cellular receptor, CD4, in an attempt to harness this interaction and the resulting conformational change in gp120 for the construction of a novel immunogen for HIV-1.
Chen Piller completed her B.Sc. in Biology at the Department of Life Sciences, Ben-Gurion University of the Negevin 2012 and proceeded to complete her M.Sc. studies at the Department of Zoology, Tel Aviv University, in 2015. Since starting her Ph.D. in 2016, at the Department of Cell Research and Immunology, Tel Aviv University, she is focusing in generation of novel Epitope-based vaccine candidates, developed to specifically focus the immune response towards neutralizing viral epitopes.
1George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel
2Sackler Faculty of Medicine, Tel Aviv University, Israel
3Kaplan Medical Center, Israel
Hepato cellular Carcinoma and Cirrhosis are often the result of viral infections and in particular Hepatitis B and Hepatitis C viruses. The prevalence of these infections is very wide spread and estimated to exceed 300 million people worldwide. The immune response towards these infections can be complex and whereas some individuals deteriorate to malignant disease, others can actually clear the infection. The correlates for effective clearance are not known and could be associated with specific antibodies directed towards the viral antigens. We have developed a novel approach to profile the antibody response towards Hepatitis C virus, and have conducted a pilot study analyzing clinical samples that represent a number of disease situations. Our methodological platform stems from combining three serological methods developed in our lab: Combinatorial diagnostics, Deep-panning and Domain-scan libraries. Here we have developed specific Domain-scan libraries representing epitopes of HCV antigens. These have been screened against HCV positive polyclonal sera. The signature responses toward specific domains will be described and discussed in relation to the clinical status of the HCV infected individuals. Understanding the details of the humoral response towards cancer causing viruses may assist in prognosis on the one hand and better designing therapeutic regimens on the other.
Biography:
Smadar Neeman completed her B.Sc. in Biology at the George S. Wise Faculty of Life Sciences, Tel Aviv University in 2011 and proceeded with her studies in the Direct Ph.D. program at the Department of Cell Research and Immunology, Tel Aviv University. Her Ph.D. research focuses on developing a novel approach to profile the antibody response towards Hepatitis C virus in order to understand the details of the humoral response towards cancer caused by viruses.
Michael Mordekovich completed his B.Sc. in Biology at the George S. Wise Faculty of Life Sciences, Tel Aviv University at 2015 and proceeded with his M.Sc studies at the Department of Cell Research and Immunology, Tel Aviv University. Michaelʼs research focuses on “Domain Scan” analysis and use of Next Generation Sequencing in profiling the human immune response towards virus infections.
1Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Republic of Korea
2Kyung Hee University, Republic of Korea
The proliferation of pre-B cells is known to increase further the clonal diversity of B cells at the stage of pre-B cells by allowing the same rearranged heavy chains to combine with differently rearranged light chains in a subsequent developmental stage. Crlz-1 (charged amino acid-rich leucine zipper-1) was found to control this proliferation of pre-B cells by working as a Wnt (Winglessrelated MMTV integration site) target gene in these cells. Mechanistically, Crlz-1 protein functioned by mobilizing cytoplasmic CBFβ (core binding factor β) into the nucleus to allow Runx (runt related transcription factor)/CBFβ hetero-dimerization. Runx/CBFβ then turned on its target genes such as EBF (early B cell factor), VpreB and λ5 and thereby pre-BCR (pre-B cell receptor) signaling leading to the expression of cyclins D2 and D3. Actually, the proliferative function of Crlz-1 was demonstrated by not only Crlz-1 or β-catenin knock-down but also Crlz-1 overexpression. Furthermore, the mechanistic view that the proliferative function of Crlz-1 is caused by relaying Wnt/β-catenin to pre-BCR signaling pathways through the regulation of Runx/CBFβ hetero-dimerization was also verified by employing niclosamide, XAV939 and LiCl as Wnt inhibitors and activator, respectively.
Biography:
Sung-Kyun Park received his PhD in Immunology from Kyung Hee University in 2011, working with Prof. Chang-Joong Kang and then worked as a postdoctoral researcher with Drs. William Garrard and Nicholas Conrad at University of Texas Southwestern Medical Center in 2016. He is currently Researcher as a principal investigator of Infectious Disease Research Center at Korea Research Institute of Bioscience and Biotechnology (KRIBB). He has contributed greatly to the understanding of molecular mechanisms in B cell development and function. Now, his work is also focused on finding new mechanism for the regulation of B cell function especially in metabolic syndrome.
1Institute of Biomedical Engineering, Taiwan
2Graduate Institute of Immunology, National Taiwan University, Taiwan
Objective: To evaluate whether antitumor immunity is enhanced systemically by combining pulsed-wave ultrasound hyperthermia (pUSHT) and local injection of an immunostimulant, OK-432.
Methods: BALB/c mice were inoculated with CT26-luc-GFP tumors on both flanks as a bilateral tumor model. The treated-side tumor underwent a 10-day treatment with pUSHT and/or subcutaneous injection of OK-432. The untreated-side tumor was used to assess the degree of anti-tumor immune response systemically induced by different therapeutics. In a rechallenge tumor model, a rechallenge tumor was implanted contra laterally after the treated-side tumor experienced a 5-day treatment and then surgically removed. This model was designed to evaluate the establishment of a long-term active tumor-specific immune memory for preventing tumor recurrence.
Results: The tumor growth rate and growth activity of both treated and untreated tumors were significantly inhibited with the OK+pUSHT combination treatment. Systemic anti-tumor effect seemed to be prolonged. The results of IF and H&E staining showed that there was a remarkable increase of NK cell infiltration in the tumor and an earlier necrosis area for the combination treatment. Survival rates significantly increased for the OK+pUSHT group. In the rechallenge test, the volume of all reimplanted tumors decreased and then disappeared as compared with the control group.
Conclusion: Combining pUSHT with local injection of immunostimulant OK-432 for a local tumor treatment may lead to activation of systemic antitumor immunity.
Biography:
Win-Li Lin received his Ph.D. degree from the University of Arizona, USA, in 1990. He joined the faculty of National Taiwan University in 1992 and became a full professor in 2001. He has been interested in biomedical engineering research, particularly in the area of ultrasound thermal therapy for tumor treatment, blood-brain barrier disruption with focused ultrasound and microbubbles, targeted nano drug delivery with focused ultrasound for central nervous system diseases and tumors, and development of high-power ultrasound devices for medical uses with magnetic resonance imaging guidance. Recently, his research is focused on developing methods to kill the primary tumor, including cancer stem cells, and the metastatic tumors.
Department of immunology, Clinic St Therese, UHC Annaba, Algeria
Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis comprises microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). Major target antigens of ANCA associated with vasculitis are myeloperoxidase (MPO) and proteinase 3 (PR3). MPO-ANCA is related to MPA and EGPA, and PR3-ANCA is the marker antibody in GPA.
Objective: Report the clinical-immunological characteristics of 92 patients with positive ANCA vasculitis.
Material and Methods: 92 patients (64 Female at 28 male), with ANCA vasculitis according to the Chapel Hill classification. ANCA was performed by indirect immune fluorescence, supplemented by immunodot to determine their specificity MPO/PR3.
Resultants: The mean age of patients was 51 years, the diagnosis was: 14 cases of GPA, 21 cases of microscopic polyangiitis (MPA), 04 cases of EGPA, 53 subjects had signs of overlap between the GPA and MPA. The clinical picture was dominated by renal disease followed by lung disease and rheumatologic signs. Some patients had cardiac involvement. 71 patients had p-ANCA (77, 17%), of which 43 were anti-MPO specificity (46.73%), and 21 patients had c-ANCA (22.83%), including 9 with a specific anti-PR3 (9, 78%), patients showed no 2 searched specificities (44.44%).
Conclusion: ANCA vasculitis is rare, clinical and immunological spectrum is very heterogeneous. The demonstration of ANCA directed vis-a-vis PR3 and MPO specific as an aid in the diagnosis of systemic vasculitis.
Biography:
Dr. Gadiri Sabiha has completed her PhD from Medicine Faculty in Annaba, Algeria and postdoctoral in immunology from Medical Faculty Annaba, Algeria. She is the headmistress of unit of autoimmunity, Clinical Hospital St Therese, Annaba, Algeria and a veteran member of the Pasteur Institute Algeria. She as a founder of Algerian society of Immunology and deputy treasurer of Algerian society of Immunology. She has participated at scientific internationals manifestations in Algeria, Tunisia, Morocco, Italia, Austria, France, Germany.
Saudi Arabia
CD1 molecules are MHC-like glycoproteins class I implicated in presenting different glycolipids to antigen specific T and NKT cells. Five genes have been identified CD1a, CD1b, CDc, CD1e and CD1d. Few polymorphic sites were reported in these genes and the functional polymorphisms were mapped in exon 2 encoding for the alpha 1 domain. The aim of this study was to investigate the distribution of exon 2 polymorphisms of CD1a and CD1d in Saudi population and their association with colon cancer disease (CC). Typing for the polymorphic sites was performed using PCR-SSP through a standardized protocol. Frequencies of CD1a*01 and CD1a*02 among healthy individuals were 42% and 89% respectively. Those of CD1d *01 and CD1d*02 were 100% and 45% respectively. These results show that frequencies of CD1a *02 (89%) and CD1d *01 (100%) are in the range of the almost reported frequencies worldwide. However, frequencies of CD1a *01 and CD1d *02 are quite larger than all reported frequencies until now. The frequency of CD1a *02 was significantly less frequent in CC patients (58.6%) (OR = 0.17; CI = 0.079-0.38 and P < 0.0001). The homozygotes CD1a *02/*02 were also less frequent in CC patients (40%) than in controls (58%) (OR=0.48; CI = 0.25-0.89 and P = 0.028). The CD1d*02 allele occurs less frequently in CC individuals (14%) compared to controls (OR=0.48; CI = 0.25-0.89 and P<0.00011). These results show potential protective effect of CD1a*01 and CD1d *02 gene against colon cancer disease in Saudi population.
Federal Fluminense University, Brazil
Background: Malaria is the most devastating protozoan disease afflicting humans. The most widespread human malaria parasite, causes 130–390 million clinical episodes. Although the pathophysiology of vivax malaria remains poorly understood. The cytokines was reported to be of importance in human malaria include TNF-α, IL-6 and IL-10, but the mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear.
Materials and Methods: We aimed to investigate participation of the cytokines in the immune response to P. vivax infection in a gold-mining area. The serum cytokine levels was assumed from 50 malaria patients and 79 healthy individuals of Itaituba, municipality situated on southwest of Para state. The plasmatic cytokines IL-2, IL-4 IL-6, IL-10, TNF-α and IFN-γ were quantified by BD Human Th1/Th2 cytokine Kit II and all purchased from BD Biosciences Pharmingen. The statistical analyses were carried out using the Graph-Pad Prism software, version 6.0 and the existence of association was determined by Mann-Whitney test, with level of significance of 0.05.
Results: Data analysis indicated significant increase in the TNF-α, INF-γ, IL-6 and IL-10 plasmatic levels (3,54 pg/mL ± 3,99; 13,80 pg/mL ± 41,52; 217,62 pg/mL ± 534,91; 1.030,44 pg/mL ± 2.290,77, respectively) in malaria group as compared with endemic control group (1,86 pg/mL ± 2,67; 4,48 pg/mL ± 17,93; 9,67 pg/mL ± 16,69; 2,22 pg/mL ± 5,20, respectively); no significant differences were detected in the IL-2 and IL-4 plasmatic levels between the groups.
Conclusions: Cytokine responses reflect different host strategies for controlling infection in different endemic areas. Our findings showed significant differences in TNF-α, INF-γ, IL-6 and IL-10 levels produced in association with parasite burden, which itself is related to the clinical course. However, the cytokine balance needs to be evaluating in different areas and population.
Keywords: Malaria, P. vivax, Cytokine, Immune response.
Biography:
Ricardo Luiz Dantas Machado, Ph. D. is a Full Researcher at Malaria Immunogenetics Laboratory of the Evandro Chagas Institute, Brazilian Ministry of Health. He received his degree in Pharmacisty from Universidade Federal Fluminense, Niteroi, Brazil in 1984 and his Ph.D. in Parasitology from Universidade Federal do Para, Belem, Brazil in 2001. He is an Associate Editor of the BMC Infectious Diseases, and serves on the editorial board of ISRN-AIDS and World Journal of Clinical Infectious Diseases. His main fields of research are coccidian diagnosis, molecular epidemiology and host-parasite relationship. He has published several scientific peer-reviewed papers, reviews and book chapters.
1Laboratory of Cellular Biology and Molecular(LBCM), Algeria
2Department of Biology, Faculty of sciences, University of Boumerdes, Algeria
3Ophthalmology Service, Algeria
Objectives: To investigate the Th1 cytokines and nitric oxide production in different types of manifestations of Behcet disease and the effect of anti-TNFα treatment on IL12 and NO induction in PBMC from Algerian patients with BD.
Methods: Peripheral venous blood was drawn from 93 patients with different type of manifestation of Behcet disease and from 63 controls. Cytokine concentration was measured by ELISA and NO levels were assessed by modified Griessʼs method. Cells were cultured with or without anti-TNF-α. IL-12 levels were measured by specific enzyme-linked immunosorbent assay. Nitric oxide levels were evaluated using a modified Griess method.
Results: Our results showed that patients with active disease had significant elevation of IL-12 and NO concentrations compared with controls. Cytokine and NO production profiles are specific to the clinical manifestation. Treatment with anti-TNF α did not reduce significantly the number of PBMC secreting IL12 in all type of manifestation studied. Further, anti-TNF-α induced significantly reduced production of NO in cell culture supernatants; a favorable clinical response to anti-TNF α was associated with Uveits and Neurobehcet manifestations.
We observed that cytokine and NO production profiles are specific to the clinical manifestation, this specificity suggests the involvement of different specific T cell populations in the regulation of immune responses occurring during active Behcet disease. These cells are probably specific to local auto-antigens.
A single infusion of anti-TNF significantly did not reduce the number of PBMC secreting IL12 in all type of manifestation studied. Anti-TNFα treatment induced a significant decrease the levels of nitric oxide production this modulation was specific to the clinical profile, a favorable clinical response to anti-TNF α was associated with Uveits and Neurobehcet manifestations.
Conclusion: These results suggest the implication of the IL12 and nitric oxide in physiopathology of BD. Our findings indicate that TNF- α plays a pivotal role in BD, and that anti-TNF- α therapy reduces NO production and may play a protective role against inflammation specially in uveites and neurobehcet manifestations.
Biography:
Dr Messaoudene Djamel is a chief at the Department of Biology, Faculty of Sciences, University of Boumerdes (UMBB) and Senior Research Fellow at the Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO-synthase team, University of Sciences and Technology Houari Boumedien, Algeria.
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