Webinar on Immunology Research October 13-13, 2020 London, UK

Biography:

Arije Ghannam, MD PhD is Doctor of Medicine, Immunologist. She obtained her doctorate in immunology at Université Claude Bernard Lyon1, and trained in innate immunity. her scientific career in immunology was developed on complement and kinins, with special emphasis on inflammation associated diseases. She is expert for kinin system, with innovative activity and licensed patents, and was awarded for OSEO innovation prize 2012. She manages the scientific team in KininX, defines and implements R&D programs.

Abstract:

The emergence of clinical Angioedema (AE) is subsequent to Bradykinin (BK) production, with AE attacks resulting from a local endothelial permeability in the affected tissue. Kallikrein-Kinin System (KKS) and BK generation mediate this process. AE with normal C1Inhibitor (C1Inh) is difficult to diagnose. It is known to be unresponsive to treatment with antihistamines, corticosteroids, and epinephrine. AE with normal C1Inh is divided between patients with a known F12 mutation and recently with plasminogen or angiopoietin mutations and those with unknown origin. However, when the patient presents with an acute crisis, the biological profile is of great support for the decision of treatment and follow-up. Here we describe four patients admitted at the acute phase of angioedema in emergency department: abdominal cramps, respiratory distress, AE of the eyelids, tongue and lips. The diagnosis was often delayed. Despite the fact that one of the patients needed tracheal intubation in the past, he suffered from recurrent AE, without diagnosis, for the last 25 years. We believe that KKS biological workup is helpful. Three samples were harvested at different times during the attack and investigated. C1 Inhibitor (C1Inh) function, spontaneous amidase activity, kinin measurement and kininogen cleavage were analyzed as described previously. The results demonstrate that KKS activation and subsequently BK production are the key actors of these attacks, without decrease of C1Inh function. They also demonstrated a very important increased kinin forming process with increased spontaneous amidase activity in line with kininogen (HK) cleavage. In addition, the administration C1Inh concentrate results in clinical improvement. The symptomatology of angioedema is subsequent to the enzymatic activity responsible for kinin production. Kinetics of biological events demonstrates KKS activation and BK production. Laboratory confirmation using KKS biological parameters seems to be helpful for diagnosis and patients management.

Biography:

Soma Mondal Ghorai has completed her PhD from University of Delhi and currently working as Assistant Professor in the Department of Zoology, Hindu College, University of Delhi, India. She has published more than 10 papers in reputed journals and has been actively involved in research in Comparative Immunology

Abstract:

Toll‐Like Receptors (TLRs) are most studied class of Pattern Recognition Receptors (PRRs) which recognize exogenous Pathogen‐Associated Molecular Patterns (PAMPs) and endogenous Damage-Associated Molecular Patterns (DAMPs) and are prime sentinels of innate immunity. Reptiles being the non-conventional model organisms remain a under deprived class in the study of structure, function and ligand specificity of TLRs except few studies published very recently. Among them, TLR5 is the only protein sensing receptor playing an inevitable role in the signaling cascade involved in innate immunity by recognizing bacterial flagellin. The unavailability of structural and ligand binding information of this receptor till date; directed us to model its ligand binding domain and docking with flagellin. Presence of several homologous proteins having considerable identity and coverage enabled us to construct a reliable 3D model of TLR5 ligand binding domain of Indo-Asian wall lizard Hemidactylus flaviviridis (hfTLR5). Experimentally, solved crystal structure of Zebrafish TLR5-N14VLR in complex with Bacillus subtilis flagellin (bsflagellin) was used as template to carry out template based molecular docking studies. Comparative analysis of docking energies and protein–ligand interactions of all the ligands revealed that bsflagellin residues interact with hfTLR5 ligand binding domain through hydrogen-bonds and hydrophobic interactions positionally segregated at two interfaces which lie in previously reported potential interacting region of TLR5. The described side chain of hot spot residue bsflagellin ‘R89’ was found to make maximum contacts and is shown inserted within the cavity formed by hfTLR5 interacting residues. Out of six, three residues of hfTLR5 (H264, G267 and N274) were found to be conserved in almost all the vertebrate classes and four out of six residues of flagellin were found to be identical in flagellins of TLR5 activating bacteria. The complex thus obtained may help us to better understand the functioning of hfTLR5, thereby bridging the gap in the evolution of species-specific host-microbe interactions.

Biography:

Daifulah Alzahrani has completed his Bachelor of degree of Medicine and Surgery from King Saud University and Pediatric Residency training Program from University of B.C. Vancouver, Canada. He is currently working as a Consultant in Allergy, Immunology and BMT at King Saud Bin Abdul-Aziz University for Health Sciences, Saudi Arabia.

Abstract:

Tuberculosis (TB) is considered by WHO as global health emergency in 1993. In 2011 one third of the world’s population was thought to be infected with TB and 8.7 million cases of active TB annually. BCG vaccine is one of the effective control measures to prevent TB. It is in practice since 1960s where TB is highly prevalent and 120 million BCG vaccines are given annually that is effective in preventing severe disease of extrapulmonary TB. However, BCG vaccine is live attenuated vaccine that potentially could cause infection, with an incidence between 1:10,000 to 1:1,000,000 and significantly higher when given to immunodeficient infants. Immunodeficient infants who receive BCG vaccine at birth could develop disseminated BCGitis, which is associated with high morbidity and mortality. However, those who develop disseminated BCGitis usually require hospital admissions and multiple medications with high cost and low survival rate ranging between 0% to 65% worldwide. Our center; KAMC-WR, Jeddah Saudi Arabia, has 83% survival rate of treating patients with disseminated BCGitis, but with using cytokine therapy and aminoglycoside drug in addition to common anti-TB drugs. There is high rate of Primary Immunodeficiency Diseases (PID) in the Middle East and Ministry of Health in Saudi Arabia recently succeeded in moving the BGC vaccine to 6-month of age, instead of giving it at birth, in order to have time for diagnosing PID. WHO considers the development of new TB vaccines a major public health priority. BCG vaccine is one of the effective preventive measures of TB; however, it could cause serious complications with low revival rate. Moving the BGC vaccine to 6-month of age will give time for diagnosing PID. Using cytokine therapy and aminoglycoside drug in addition to common anti-TB drugs will significantly reduce mortality and morbidity. There are potentials for development of new BCG vaccine.

Biography:

Lang Bao is currently working as a Professor in Microbiology and Immunology. He has completed his PhD from West China University of Medical Sciences in 1999 and then moved to WHO Collaborative Research Centre of Infectious Disease, Royal Tropical Institute, Netherlands for his Post-doctoral training. He has published around 100 research papers.

Abstract:

Introduction: Tuberculosis (TB) is a serious infectious disease caused by M. tuberculosis. BCG had been considered to be the only available and effective vaccine in prevention of TB. However, the protective efficacy of BCG on TB was still controversial in different populations and age. Thus, improved TB vaccines are urgently needed to develop as an alternative to BCG which was able to activate immune response and protect against severe forms of TB effectively.

Method: Two BCG strains (Pasteur and Shanghai) were used parental strain and specific antigens of M. tuberculosis Ag85A, CFP10, ESAT-6 and immune regulation cytokines GM-CSF, IL-12p70 were integrated into BCGs respectively. BALB/c female mice were immunized subcutaneously with single-gene rBCGs and multiple-gene rBCGs. The specific antibody levels of lgG, lgG1 and lgG2a in immunized mice were detected by ELISA assay. Detection of proliferation of splenic lymphocytes and splenocytes subsets by flow cytometry were conducted. Nine rBCG strains were chosen for protective efficacy test. After eight weeks of immunization with rBCGs, mice were challenged intravenously by M. tuberculosis H37Rv. Histopathological examination and bacterial load was performed on the lung, spleen tissues of immune mice. Results: Both single-gene rBCGs and multiple-gene rBCGs could induce strong humoral and Th1 cellular immune reaction. Significantly higher levels of Th1 cytokines IFN-γ was revealed in both multiple and singlegene rBCGs, while Th2 cytokines IL-4 was not detected in all rBCGs. After 18 weeks, the survival rate was 100% in rBCG- Pasteur: A, rBCG- Pasteur: AE and 80% in rBCG-SHanghai: IE, rBCG-Pasteur: GC only 60% in rBCG- Pasteur: GCE.

Conclusion: rBCG had excellent immunogenicity and immune protective efficacy. It could regulate the level of TNF- alpha by p38 MAPK and NF-kB signaling pathway and induce the apoptosis of macrophages. BCGPasteur is more suitable for parental BCG than the BCG-SHanghai. These findings can provide ideas and experimental basis for the development of anti-tuberculosis recombinant vaccines.

Biography:

Yalda Hassanpour has completed her Medical degree from Mashhad University of Medical Sciences, Faculty of Medicine, Iran

Abstract:

Since avoidance of triggering agents is the most important step in the management and prevention of allergic reactions, identifying the causes of anaphylaxis which is an acute, potentially fatal systemic reaction is very important in every community. In this cross-sectional survey we evaluated all patients with a history of anaphylactic reaction, being referred to allergy clinics of two tertiary university hospitals of Iran between 15 April 2010 and 5 January 2017. We used a combination of the patient’s clinical history and allergy diagnostic testing including SPT and RAST to determine the etiology of anaphylaxis. We identified 172 anaphylactic reactions in 70 patients. Of the patients, 44.3% were adults and 55.7% were male. Median age was 15 years; range was from 6 months to 48 years. The triggers included: foods, 61.4%; drugs, 15.7%; hymenoptera venom, 8.6%; idiopathic, 5.7%; immunotherapy, 4.3%; other, 5.7%. Atopy was present in 2/3rds of the patients and a positive family history of anaphylaxis in 2.9%. Nuts and seeds were the most important triggers of food induced anaphylaxis, especially in schoolchildren, adolescents and young adults, followed by fruits. However, cow's milk and hen's egg were the only triggers of anaphylaxis in children under 2 years of age. The most common symptoms were cutaneous (85.7%) and cardiovascular (77.1%). Corticosteroids (94.3%) and/or antihistamines (85.7%) were used most frequently for treatment followed by intravenous fluids (54.3%), whereas Epinephrine was only used in 17.1% of the cases. Based on our findings in this study, food-related anaphylaxis and other typical triggers of anaphylaxis are age-dependent and the risks and triggers change with age.

Biography:

Amal Aldawi Assistant professor in Immunology Ibn Sina University. Certified Immunologist American Board Bioanaylysis (ABB). She earned her master and ph.D degrees in immunology from Khartoum university institute of endemic disease . She is an expert in histocompatibility analysis and the analysis of cellular immuntiy to infectious diseases.she is a leader in tissue culture of leishmania parasite and invitro stimulation of periheral blood and cytokines analysis. She works on several research projects at Bioscience Research Institute Ibn Sina University and supervised several junior scientists and postgraduate students.She has built after years of experience in research evaluation,teaching and administration in education institutions.

Abstract:

Protozoa of the genus Leishmania cause a wide variety of pathologies ranging from self-healing skin lesions to visceral pathology. The outcome of infection depends on the species of the infecting Leishmania parasite. A significant role of the adaptive immune response was described for the development of clinical disease and cure. While TH2 was associated with development of clinical disease, TH1 response was associated with cure. This study aimed to determine the profile of innate immune markers using Leishmania infected human THP1 macrophage cell lines. The parasite isolates were collected from patients suffering from cutaneous, visceral, post kala-azar dermal and mucosal leishmaniasis. Human THP1 cells were infected by live promastiote of Leishmania donovani isolates from Cutaneous (CL), Visceral (VL) and Post Kala-Azar Dermal Leishmaniasis (PKDL) and Mucosal Leishmaniasis (ML) patients. The expression of toll like receptor TL22, TL4 and TL9 and expression of IFN-γ and IL-10 cytokine was measured using Real Time PCR. The production of IL-1ß, IL-6 and TNF-α cytokines was measured using captured ELISA. A significant increase in the expression of TLR 2, TLR4 and TLR9 by L. donovani infected THP-1 from ML patients was detected. A higher concentration IL-6 and IL-1β was detected in supernatants of L. donovani infected human macrophage cell lines from CL patients compared with VL and ML patients whereas IL-1β concentration was higher in L. donovani infected human macrophage cell lines from ML patients. Our data measured a significant increase in the expression of TLR 2 and TNF-α by THP-1 cell line infected with L. donovani isolate from mucosal patient. Leishmania isolates from mucosal and PKDL patients induced significant gene expression of TLR 4 and TLR9. These results could contribute to better understanding of the dynamics of gene expression and production of coinflammatory cytokines in host cells during leishmaniasis.

Biography:

Charles J Malemud received the PhD from George Washington University in 1973 and completed postdoctoral studies at the State University of New York at Stony Brook in 1977. Since 1977, he has been a member of the faculty at Case Western Reserve University School of Medicine where he is presently Professor of Medicine & Anatomy in the Division of Rheumatic Diseases and Senior Investigator of the Arthritis Research Group. He has published over 230 papers, chapters and reviews primarily in the field of chondrocyte biology. He is on the editorial board of rheumatology, immunology, and musculoskeletal journals and is Editor-in-Chief of the Journal of Clinical and Cellular Immunology and Global Vaccines and Immunology.

Abstract:

The Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) signaling pathway plays a prominent role in several autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus, psoriasis/psoriatic arthritis, and, inflammatory bowel disease. Thus, the continuous activation of JAK-STAT signaling mediated by the substantially elevated levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL-17, IL-12/IL-23 and interferon-γ, to name just a few in these diseases, disrupts many of the downstream cellular events regulated by JAK-STAT signaling. This often results in the aberrant survival of immune cells and accessory cells thus perpetuating chronic inflammation. The extent to which JAK-STAT signaling is involved in these autoimmune diseases led to the pre-clinical development and clinical trials evaluation of JAK small molecule inhibitors (SMIs), now referred to as “Jakinibs.” These include tofacitinib, ruxolitinib, and baricitinib which were FDA-approved for the medical management of RA, psoriasis and myeloproliferative disease. In a pre-clinical analysis, tofacitinib demonstrated a relative selectivity for JAK1/JAK3 compared to JAK1/JAK2. At the cellular level, ruxolitinib, a JAK1/JAK2- selective SMI was shown to reduce the plasma levels of IL-6 and CD-40 as well as the phosphorylation of STAT3 ex vivo using blood cells from RA patients. Conversely, in cell-free assays, baracitinib is relatively selective for JAK1/JAK2 (IC50=5.9/5.7nM, respectively) compared to JAK3 and Tyk2 and exhibits no inhibitory activity towards either the tyrosine-protein kinase Met or checkpoint kinase-2. Baracitinib was also shown to inhibit IL-6-stimulated or IL-23-stimulated phosphorylation of STAT3 as well as the downstream synthesis of the chemokine, monocyte chemoattractant protein-1. At present, studies are being conducted by our research group to determine the extent to which tofacitinib inhibits matrix metalloproteinase gene expression by cultured human chondrocytes.

Biography:

Michael G Hanna is a co-founder of Vaccinogen, Inc., the discoverer and developer of OncoVAX, Vaccinogen’s lead project, and a pioneer in the field of cancer vaccines. He also developed and obtained FDA approval for TICE BCG for treatment of carcinoma in situ ("CIS") bladder cancer which remains the standard of care for prophylaxis of recurrence of superficial bladder cancer and therapy of CIS. He has not only proven his capabilities as discoverer and developer of clinically beneficial biotherapeutics but also has raised over $300 million for the final clinical development of OncoVAX. As the director of the National Cancer Institutes, Frederick Cancer Research Center, between 1975–1983, he created a center of research excellence and managed over 2,000 technologists consisting of hundreds of MDs and PhDs. A special committee of the National Cancer Advisory Board selected him for the above responsibilities. He previously served as Chairman (Emeritus) and Chief Scientific Officer of Intracel Resources, an integrated biopharmaceutical company that developed cancer vaccines and immunotherapeutic and diagnostic products for both cancers and infectious diseases. He also served as President and Chief Executive Officer of PerImmune, Inc. before it and Intracel Corp. merged in 1998. From 1985 to 1994, he was the Chief Operating Officer of Organon Teknika Biotechnology Research Institute and Senior Vice President of Organon Teknika Corporation, a subsidiary of Akzo Nobel, NV, The Netherlands. Prior to that, he was Director of the National Cancer Institute, Frederick Cancer Research Center. He received a doctoral degree in experimental pathology and immunology from the University of Tennessee. He has over 225 publications to his credit, has 10 patents in immunotherapy and has been the recipient of numerous honors.

Abstract:

Over the last decade, the field of cancer biology has gained considerable data on genomic heterogeneity. This situation creates challenges and possible opportunities for cancer treatment. The evolution of the tumor at all stages also requires the growing malignancy to confront and avoid the immune system. What we describe here is the interaction of two immune phenomena that work together to change the characteristics of the tumor, i.e., antigenic competition and immune editing. These two systems are mutually functional and their interaction is capable of altering the characteristics of the tumor for protection and survival in an immune competent host as well as restricting the diversity of the tumor clones. Therefore, the final outcome of these interactions can also become the key to the back door of the castle. Through an additional immune manipulation, autologous tumor cell immunization, we can achieve prevention of disease recurrence after surgical resection and by analyzing induced human monoclonal antibodies to the neoantigens, gain in site into the restriction of the diversity of the mutant clones. These findings may also open the door for a pathway to the immune prevention of cancer.

Biography:

Sharad Kumar Yadav has 30 years of teaching and research experience and has served to various senior positions of the University including Registrar of the DUVASU University. He is currently Professor, Head of Department of Veterinary Microbiology, and Director at Cow Research Institute at DUVASU, Mathura, India. He has published a number of papers in reputed International & National journals and has a vast experience in the arena of BHV-I virus.

Abstract:

Vaccines in the current scenario of a research play particular role in prophylactic, therapeutic agents in cancer, disease and different types of the infections. Synthetic nanoparticles now a day are playing a significant role in vaccines designs and development because these synthetic nanoparticles based vaccines show greater safety, efficacy, and longevity over the previously used vaccines. Nanocarriers with various biotechnological properties and structures have been used vastly both in vitro and in vivo drug and gene delivery. The groups of nanocarriers have been polymeric nanoparticles, lipid-based carriers (liposome, micelle, dendrimers, carbon nanotubes, and gold nanoparticles are some of the members of the lipid-based nanocarriers and these polymeric nanoparticles delivery system have huge properties which include these easily biodegradable, biocompatible, inexpensive, no-immunogenic, non-toxic, water soluble and most importantly easy to be synthesized. However, some obstacles still remain due to lack of real/fundamental knowledge on the detail molecular mechanism of work and in vivo bioeffects of these nanoparticles. These basic facts of the in vivo biodistribution and fate of nanoparticles will ultimately extra gate design of the new nanoparticles comprising the vaccines for the future. This keynote address is a broad overview of the current scenario in nanoparticle in vaccinology and modern vaccine development.

Biography:

Claudia Gravekamp, PhD, is an Associate Professor in the Department of Microbiology and Immunology of the Albert Einstein College of Medicine in New York, and a member of the Albert Einstein Cancer Center. She received her PhD in 1988 in the field of Tumor Immunology at the Erasmus University in Rotterdam, The Netherlands. From 1987-1993, she served as head of the Laboratory for Leptospirosis at the Royal Tropical Institute in Amsterdam, The Netherlands. In 1993, she started as a Research Fellow in Medicine at the Channing Laboratory of the Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, and soon thereafter became an Instructor in Medicine until 1998. From 1998 to 2006, she was an Associate Member in the Institute for Drug Development of the Cancer Therapy and Research Center and an Assistant Professor at the University of Texas Health Science Center, in San Antonio, TX. In San Antonio, she began to develop a program aimed at genetic vaccines for breast cancer. From 2006-2008, she was a Scientist at the California Pacific Medical Center Research Institute in San Francisco, CA. She has been funded by grants from the NIH, other grant agencies and private industry since 1999), published 65 scientific articles.

Abstract:

Our laboratory has built a platform for the selective delivery of anticancer agents to the tumor microenvironment (TME) using a live attenuated bacterium Listeria monocytogenes. We discovered that Listeria could infect and kill tumor cells through reactive oxygen species, and selectively survives and multiplies in tumors and metastases but not in normal tissues because of the strong immune suppression in the TME that is absent in normal tissues. Listeria can infect tumor cells directly or through infection of myeloid-derived suppressor cells (MDSC), which are selectively attracted to the TME through cytokines and chemokines. Once at the tumor site, Listeria efficiently moves from MDSC into tumor cells through a mechanism specific to Listeria. This novel discovery opened doors for the development of complete new therapies, particularly for non-curable metastatic cancers. We developed Listeria-188Rhenium and Listeria-32P. Both have been tested in preclinical models for biodistribution, efficacy, and safety. These radioactive Listeria bacteria strongly reduced the growth of pancreatic cancer at early and advanced stages in various mouse tumor models, with practically no side effects. We also generated Listeria-based vaccines, expressing highly immunogenic “recall antigens” (RA) derived from tetanus toxoid (TT) protein, polio virus (PV) and measle virus (MV), which in combination with low doses of Gemcitabine, resulted in the reactivation of memory T cells to RA (generated during childhood vaccination and circulating in blood for life), now capable of killing Listeria-RA-infected tumor cells, with help of Gemcitabine-reduced immune suppression. These results demonstrate the potential of Listeria as a selective delivery platform for cancer immunotherapy. Delivery of adjuvants, RNAs, apoptotic genes, small molecules by Listeria to the TME could be a promising next step in the fight against metastatic cancer.