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Keynote Speaker

Time:

Title: The Management of Advanced Colorectal Carcinoma having failed Standard Therapy – An Immunologic Approach

Myron Arlen
Monter Cancer‎ Center: Div. Northwell Health System, USA

Biography

Dr. Myron Arlen, M.D. is a Principal Founder of Neogenix Oncology Inc. in 2003 and has been its Director of Medical Affairs since March 2010. Dr. Arlen has substantial executive experience in the biotechnology industry. Dr. Arlen served as the Chief Executive Officer of Neogenix Oncology Inc. from 2003 to March 2010. Dr. Arlen served as Chairman of Neogenix Oncology Inc. and served as its Director from 2003 to January 2012. Dr. Arlen was trained as a cancer surgeon at Memorial Sloan-Kettering where he remained on staff for 20 years involved in the surgery of advanced cancer problems and the immunotherapeutic approaches to managing the patients. Dr. Arlen established the Surgical Oncology Division at North Shore University Hospital, and formed a practice group (North Shore Surgical Oncology Associates). He has written two major textbooks and published over 80 journal articles related to cancer treatment. In the 1990's, Dr. Arlen helped to found another biotechnology company, International Bio-Immune Systems, Inc. of which he was part of management until 2003.

Abstract

In order to achieve effective control ofadvanced colorectal cancer having failed standard therapeutic approaches, we are employing specific monoclonal antibodies that were developed in our facility to target oncofetal proteins expressed in this tumor system. Phase II FDA trialshave been completed in this group of patients with evidence of positive therapeutic responses. Pooled allogeneic tumor membrane protein was utilized to identify those immunogens found in colon cancer specimens with the goal of eventually employing them as therapeutic vaccines. Three oncofetal proteins that characterize colorectal Ca were identified. These proteins were evaluated for structure and the role they played in the developing malignancy. It was noted thatthey were always present in the tumor but at sub threshold levels necessary for activating the host immune system. In addition they were found to be absent in essentially all normal colon specimens examined. Because of the sub threshold levels at which the single or combination of oncofetal proteins were expressed in the malignant state an ineffective immune response that is normally present with bacteria and viruses , is unable to prevent tumor growth and subsequent progression of disease. In order to obtain the needed host immune recognition of lesions such as metastatic colorectal cancer we have found that by pooling these oncofetaltumor membrane proteins, that the proper threshold level of antigen needed toact as an effective immunogen (vaccine), can be achieved. This level has been determined to be approximately 500 ugm. of antigen delivered intradermally in 3 divided monthly doses along with an effective adjuvant. In examining levels of antigen expressed in an entire tumor specimen used in our preparations it was rare to find levels above 10-25 ugm. This explains why once malignant transformation occurs, it continues unabetted since immune suppression is not initiated by the host immune system. Among those treated using pooled antigen as a vaccine, it was found that the high rate of clinical cures seen, was not achieved by the increased number of cytotoxic T cells, but rather by the expression of high levels of an IgG1 targeting the tumor immunogen with subsequent tumor destruction via ADCC (antibody dependent cell cytotoxicity). At the 2015 ASCO GI Symposium in San Francisco, CA , results of the Phase 1 study of Neo-102 in chemotherapy refractory metastatic colorectal cancer patients revealed a Maximal Tolerated Dose of 3.0 mg/kg IV every 2 weeks. The overall survival observed in this demonstrated 10.4 months comparing favorably to the historical control for a similar population of patients with advanced colorectal Ca (5 months). This has led to a larger Phase 2 multi-center colorectal cancer study using Ensituximab(Neo-102) in the same patient population where results are being confirmed. Because tumors do shed an inhibitory molecule into the serum blocking many of the anti-tumor effects of IgG1 in its ADCC response, new trials are being designed to initiate the study somewhat earlier and with low dose chemo being added to minimize inhibitory antigen. This will follow with the eventual addition of IL-which does enhance NK cell activity.

Keynote Speaker

Time:

Title: Uncoupling Immunodominance,Antigenic Variation and Strain-restricted Immunity in developing the Next Generation of Vaccines and Monoclonal Antibodies

Peter Lloyd Nara
Biological Mimetics, Inc, USA

Biography

Dr. Nara currently is the Chief Executive Officer, President, Chairman & co-founder of Biological Mimetics, Inc. and holds the Endowed Eugene Lloyd Entrepreneurial Chair and Professor in Vaccinology, founding Center Director for the Center for Advanced Host Defense, Immunobiotics, and Translational Comparative Medicine in the Department of Biomedical Sciences, in the College of Veterinary Medicine at Iowa State University, is an adjunct professor of Microbiology/Immunology, Carver College of Medicine, University of Iowa. Dr. Nara holds a M.Sc. in Immuno-pharmacology, a combined Doctor of Veterinary Medicine and Ph.D. (retro-virology/oncogenesis) from The Ohio State University, 4 year combined residency in Comparative Pathology and NIH senior post-doctoral Fellowship at both the Armed Forces Institute of Pathology and the NIH respectively. He has received numerous awards and recognition and in 2011 was elected as a Fellow of the American Association for the Advancement of Science (AAAS) for his work related to Deceptive Imprinting and Immune Refocusing Technology.

Abstract

Over the last 250 years, the use of vaccines, a mainstay of preventative medicine and public health has proven to be one of the most successful and cost-effective medical interventions ever discovered. Despite these great advances to human and animal health of the past 5 decades; the basic immunologic principals and technology does not for the most part work against the many remaining pathogens of humans and animals. This is mainly due to a combination pf evolved host evading strategies of the pathogens and yet unappreciated aleatory characteristics inherent within the vertebrate immune system. These combined make them inherently more resistant due to strain-restricted immunity/antigenic variation/poor memory/disease-enhancement/incomplete immunity and/or shortened forms of immunity---all are a major gap in our understanding of the complex evasion mechanisms evolved by the pathogens. “Deceptive Imprinting” is at the heart of a new understanding of how the host may respond to mutable pathogens to create a molecular diversion (decoy) at the level of both the innate and acquired immune host defense systems-- much like how metallic chaff would confuse a radar system trying to locate a missile or plane. On an immunologic level immunodominance, repertoire sculpting and antigenic variation are coupled such that host immune responses are directed to more strain-restricted and less or non-protective B and T cell immune responses. To circumvent this host evading mechanism we have developed a first generation technology called Immune Refocusing that has been designed specifically to reorder the non-protective immunodominance by identifying/mapping the decoy epitopes and molecularly removing or attenuating it thus redirecting the host immune system to the more protective regions of the microbe. This lecture will bring together new paradigm shifting first principals of Deceptive Imprinting, immunology, new insight from querying pathogen genomes through “Pressure Point” Technology and application of the technology of Immune Refocusing. These paradigm shifting scientific insights have opened up fresh new approaches to technical advancement and the development of new antigens that can be used for vaccines and deriving new monoclonal antibodies toward inducing improved and broader protective immunity.

Sessions:
Veterinary Vaccines & Influenza and Respiratory Vaccines
Emerging and Re-Emerging disease & Plant based Vaccines & Cancer vaccines and Immunotherapy
Recombinant Vaccines and Therapeutic Vaccines

Time:

Title: Recent advances in host protective immunity and novel disease control strategies against intestinal protozoan infections in commercial poultry

Hyun Lillehoj
USDA, USA

Biography

Dr. Lillehoj received her B.S. degree in Biology from the University of Hartford, M.S. degree in Microbiology from the University of Connecticut, and Ph.D. in Immunology from Wayne State University, School of Medicine. She was a NIH post-doctoral fellow in the Department of Immunology and Microbiology, Wayne State University to conduct research on cancer immunology and immunogenetics of autoimmune diseases. From 1981 to 1984, she was a staff fellow in the Laboratory of Immunology, NIAID, NIH where she studied T-cell immunity. Since 1984, Dr. Lillehoj worked at the Beltsville Agricultural Research Center. She was promoted to the Supergrade (ST) in 2004. Her research career has focused on mucosal immunity, vaccines, immunogenetics and antibiotic alternatives. Dr. Lillehoj developed the first set of commercialized mouse monoclonal antibodies detecting chicken lymphocytes, constructed the first chicken intestinal cDNA microarray which has been of seminal importance in national and international poultry genomics research and developed and commercialized many novel antibiotic alternative strategies. Her research has resulted in more than 404 original papers, 20 book chapters, and 13 national and international patents. She has been awarded more than $ 20 million in research funding, including 8 CSREES NRI, BARD, IFASA, and Food Safety Initiative grants, and 45 formal collaborations (CRADAs) with private industry. In addition, she has served on numerous editorial boards, national grant panels, award and technical committees, and chaired multiple sessions at national and international meetings. Dr. Lillehoj holds guided the research of 130 junior scientists from 13 different countries. Her accomplishments have been recognized by the BARC Technology Transfer Award (1998), the ARS Technology Transfer Award (1999), the Federal Laboratory Consortium (FLC) Technology Transfer Award (1999), the Helen Cecil Leadership Award (2001), Pharmacia/Upjohn Animal Health Achievement Award (2001), Beltsville Agricultural Research Center Senior Scientist of the Year Award (2003), the ARS Outstanding Scientist of the Year Award (2004), Merck Achievement Award (2006), the Levine P.P Award (2006), the Pfizer Animal Health (Embrex) Fundamental Science Award (2007), Beltsville ARS Technology Transfer Award (2008), and Phibro Animal Health Award (2011). Dr. Lillehoj was selected to receive 2014 Distinguished Veterinary Immunologist by the American Association of Veterinary Immunologist. Dr. Lillehoj was inducted into the ARS Hall of Fame in September 2014 and is the winner of 2015 Presidential Rank Award. In 2015, she has been selected as the winner of the American Service Medal for Career Achievement Award.

Abstract

Poultry meat consumption has increased globally by 50% since 2000, accounting for greater than 100 million tons in 2012. Multiple challenges confront the rising demand for poultry food products, including governmental restrictions on the use of antibiotic growth promoters and novel feedstuffs, high-density production conditions, waste management, and the emergence of infectious pathogens, particularly those that cause intestinal diseases. There is little doubt that in-feed antibiotics has dramatically increased the efficiency of commercial poultry production over the last 50 years. However, antibiotic usage in chickens has raised consumer concerns regarding chemical residues in the poultry products that they consume, and has directly led to the appearance of drug resistance among avian pathogens that has the potential to be transferred to microorganisms that infect humans. Much interest, therefore, has focused on the development of alternative, antibiotic-free methods of commercial poultry production. These newer disease control strategies can be broadly classified into those that are directly cytotoxic against infectious agents, including hyperimmune antibodies, antimicrobial peptides, and bacteriophages, and those that augment host immunity, including phytochemicals, adjuvants, and next-generation vaccines. This talk will highlight new approaches which are being developed to protect against avian coccidiosis using passive and active immunization strategies. Keywords: chicken, Eimeria, antibiotic alternatives, gut, disease

Time:

Title: Clostridium perfringens, Necrotic Enteritis and Its Vaccination in Broiler Chickens

Charles Li
USDA, USA

Biography

Charles Li is a research veterinary medical officer and PI in ARS/USDA. He has DVM and MS in veterinary microbiology, and received his doctorate in animal immunology at the Ohio State University. He performed the novel HIV-vaccine research using attenuated Listeria monocytogenes as vaccine vector and RNA vaccine at University of Pennsylvania. Thereafter his working experience ranges from multidrug resistance bacteria, vaccine development for infectious diseases, cancer therapy and biosafety testing management at several large institutions in US. His current research programs focus on vaccine development for necrotic enteritis, avian immune reagent development and gut microbiome studies in metagenomics and transcriptomics tools.

Abstract

Clostridium perfringens type A strains are the main etiological factors for necrotic enteritis (NE), one of the economically important gastrointestinal diseases in poultry responsible for the annual loss of 2 billion dollars in US poultry industry. NE has gained worldwide attention during the last decade. The increasing occurrence of NE is thought to be associated with withdrawal of antibiotic growth promoters from the feed. Many predisposing factors, such as high levels of proteins in the feed, coccidiosis co-infections, immunosuppression, have been found to enhance this disease occurrence. Several infection models will be discussed. C. perfringens culture supernatant infusion alone, in the absence of bacterial cells, was found to affect the pathways related to disease pathogenethesis by inducing expression of genes related to early immunomodulation, inflammation and cell death in the small intestine. Vaccination with modified toxins or other immunogenic antigens seems a logical strategy for such disease prevention. Several vaccine strategies are presented. The most important immunogenic and protective proteins have been tested in several vaccination studies, including alpha toxin and NetB toxin. The combinations of different immunogenic antigens including NetB toxin should be required to protect birds against the severe challenge. Key words: Clostridium perfringens, Necrotic Enteritis, Vaccine, Broiler Chickens

Time:

Title: Documenting the need for Routine Influenza Vaccination in Kenya; A Case of Influenza associated severe acute respiratory illness outbreak, Nakuru County, Kenya

Elizabeth Kiptoo
Department of Health Services, Kenya

Biography

Elizabeth kiptoo is a holder of Master of Public health Epidemiology and disease control at the age of 43 years from Mount Kenya University. Has worked in the field of public health for the last 22 years. She is a member of faculty associate of Mount Kenya University. A young researcher who has published two papers in reputed journals.

Abstract

Severe Acute respiratory illness continue to be the leading cause of acute illnesses worldwide and remain the most important cause of morbidity in children less than one year. Influenza A and B viruses are among the most common causes of respiratory tract illnesses among children. Influenza surveillance in Kenya describes the incidence and prevalence of influenza among patients with ILI, SARI, and ARI. Influenza accounts for up to a quarter of ILI cases, a tenth of SARI cases and up to half of all ARI cases. Influenza vaccination is the main strategy of prevention, but influenza vaccination is not in the Routine immunization Schedule in Kenya. The purpose of this study therefore is to demonstrate the burden of influenza associated SARI and document the need for introduction of influenza vaccine into the routine immunization schedule. The study was conducted in Nakuru county referral hospital located in Nakuru County which is one of the 47 counties of the Republic of Kenya. A retrospective analysis of SARI outbreak data that was collected during the outbreak between March and June 2016. Case definition was used to identify cases. SARI cases were entered into an excel line list. Data Analysis was done using SPSS version 20. Chi square tests were used to establish association of relevant risk factors with the occurrence of influenza associated SARI. All confidence intervals (CI) were maintained at 95%. Statistical significance was defined at p 0.05. The outbreak began in week 9 of 2016 in Nakuru North as epi centre and eventually spread to the entire County. A total of 823 cases with 94 deaths were reported. All sexes were equally affected. Children less than 2 years were mostly affected and high mortality recorded amongst children less than one year. Nasopharyngeal swabs samples were analysed in 5 laboratories. Results indicated that 42% were as a result of RSV, 30% influenza A and B, 12% did not yield any pathogen and the rest were as a result of other viruses. Important risk factors identified included Co-morbidities (X 1716.7, p 0.000), non vaccination with influenza vaccine X 1702, p 0.000) and malnutrition (X 1379, p 0.000). The prevalence of Influenza among sari patients is high, comobidities, non vaccination and malnutrition are the major risk factors. It is necessary to introduce influenza vaccine into routine immunization schedule and to carryout another study to determine the prevalence of malnutrition and associated factors so as to form the basis for intervention

Time:

Title: The current status and need for therapeutic vaccines for autoimmune conditions with emphasis on arthritis

Dan Zimmerman
CEL-SCI Corporation, USA

Biography

Daniel H Zimmerman, Ph.D is the head of the L.E.A.P.S. technology program. Dr. Zimmerman has invented technologies which are covered by over a dozen US patents as well as many foreign equivalent patents. He has been involved in the development and commercialization of several successful products licensed by FDA for HIV and HBV as well as other products in other areas. He is the author of over 50 scientific publications starting with his work in the laboratory of Milton Kern at NIH in the areas of cellular immunology, immuno-diagnostics, infectious diseases, autoimmune conditions and vaccine design. He has been awarded numerous grants from NIH and DOD in these areas. In addition he is, or has been involved with numerous scientific collaborations at multiple institutions in the US.

Abstract

Background. Rheumatoid arthritis (RA) is an autoimmune disease leading to inflammatory destruction of the peripheral joints. Although pro-inflammatory T helper 1 (Th1) and/or Th17 cell responses play a central role in the immunopathology of RA, current therapies do not provide efficient inhibition of these pro-inflammatory T cells or their signature cytokines. Therapeutic vaccines for RA and other autoimmune conditions (IDDM and MS) were identified before the start of this century by the Institute of Medicine as a major need. Review of the scientific and patent literature, showed that progress on a RA vaccine and the number of candidates are more limited and development slower than for prophylactic vaccines against infectious diseases in spite of the IOM report. We report some progress in our efforts for a RA vaccine effective in the PGIA and GIA models of RA, which share a number of common features with RA in man including 1) predominance in older females 2) RF and 3) ACPA not seen in most animal models. Methods. Disease was induced in older female BALB/c mice by intraperitoneal (ip) immunization with the recombinant G1 domain of human cartilage proteoglycan (PG) aggrecan in adjuvant (DDA). The CEL-4000 vaccine is a LEAPS peptide vaccine composed of an immune cell binding ligand (ICBL) from the CD4 binding domain of human MHC-II conjugated to the arthritogenic epitope of human PG (PG70). Therapy was initiated at the early phase of arthritis after visible joint inflammation was observed by two injections with adjuvant (2 weeks apart). Disease severity was monitored by visual scoring of joint inflammation. At the end of the study limbs were processed for histopathology, serum collected for measurement of pro- and anti-inflammatory cytokines and spleen cell cultures were set up to determine Th cell cytokine profiles. Results. The CEL-4000 vaccine significantly suppressed arthritis severity and limited joint damage by both visual and histopathology scoring. ALEAPS conjugate (J-PG70) with a different ICBL or single peptides were not therapeutically effective. Increased ratios of anti-inflammatory to (pro-inflammatory + inflammatory) cytokines were observed in the serum of mice vaccinated with CEL-4000 as compared to the other treatment groups. Spleen cells from mice with GIA and vaccinated with CEL-4000 showed reduced production of Th1 and Th17 signature cytokines as well as other pro-inflammatory mediators in vitro as compared to controls. Conclusions. Our results suggest that CEL-4000 down-modulates pro-inflammatory T-cell responses that suppress the root cause of RA. Work is progressing toward IND enabling studies.

Time:

Title: The results of Phase II Clinical trial of HIV therapeutic optimized DNA Vaccine: The possible reach of Viral reservoirs

Andrei Kozlov
The Biomedical Center, Russia

Biography

Andrei P. Kozlov, Ph.D., Dr.Sci., Professor of Molecular Biology, was born in Leningrad in 1950. In 1972 he graduated with honors from St. Petersburg State University (Department of Biochemistry). During the period 1972-1975, he completed postgraduate studies at the N.N. Petrov Research Institute of Oncology and successfully defended his Ph.D. thesis devoted to the studies of low molecular weight nuclear RNAs in normal and tumor tissues. In 1978-1979 Dr. Kozlov served in a tenured Research Training Fellowship awarded by the International Agency for Research on Cancer at the laboratory of Robert Gallo at the National Cancer Institute.

Abstract

The DNA vaccine consists 4 DNA plasmids which contain optimized nef, gag, rt and env genes of HIV-1 subtype A. The aim of the study was to estimate the safety and tolerability of the vaccine in HIV-infected patients on HAART. We also investigated the dynamics of viral load (including blips ≥ 50 copies/ml) and CD4+ T cells. This was a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial. Trial participants were randomized in three groups: 0.5 mg of “DNA-4” (17 patients), 0.25 mg “DNA-4” (17 patients) and placebo group (20 patients). All patients were immunized 4 times at days 0, 7,11,15 intramuscularly without electroporation followed by 24 weeks follow-up period. “DNA-4” was well tolerated. There were no deaths or severe adverse effects detected during the study. Adverse affects were more pronounced at lower DNA concentrations. Neutropenia and leukopenia were detected in four vaccinated patients. Local reactions were detected in vaccinated groups and placebo group with the same frequency. We found that 3 trial participants (in groups 0.25 mg and 0.5 mg) had significant increase in blips amplitude (18000 copies/ml and 2800 copies/ml in group 0.25 mg; 709 copies/ml in group 0.5 mg) while the frequency of blips was similar in vaccinated and placebo patients. This might be caused by destruction of latent viral reservoirs as a consequence of induction of cell immunity and expression of TNFα in vaccinated patients as shown by previous studies.

Time:

Title: The Development of Specific Cancer Vaccines targeting Colorectal and Pancreatic Cancer

Myron Arlen
Monter Cancer‎ Center: Div. Northwell Health System, USA

Biography

Dr. Myron Arlen, M.D. is a Principal Founder of Neogenix Oncology Inc. in 2003 and has been its Director of Medical Affairs since March 2010. Dr. Arlen has substantial executive experience in the biotechnology industry. Dr. Arlen served as the Chief Executive Officer of Neogenix Oncology Inc. from 2003 to March 2010. Dr. Arlen served as Chairman of Neogenix Oncology Inc. and served as its Director from 2003 to January 2012. Dr. Arlen was trained as a cancer surgeon at Memorial Sloan-Kettering where he remained on staff for 20 years involved in the surgery of advanced cancer problems and the immunotherapeutic approaches to managing the patients. Dr. Arlen established the Surgical Oncology Division at North Shore University Hospital, and formed a practice group (North Shore Surgical Oncology Associates). He has written two major textbooks and published over 80 journal articles related to cancer treatment. In the 1990's, Dr. Arlen helped to found another biotechnology company, International Bio-Immune Systems, Inc. of which he was part of management until 2003.

Abstract

We have noted in experimental studies designed to isolate and characterize the immunogen that defines colorectal and pancreatic cancer, that the transforming cell initially expresses this protein at the time of genotypic transformation prior to the appearance of those cells demonstrating phenotypic features of neoplasm. This protein is represented by a mutated oncofetal protein acting as an immunogen but at too low a level to induce a host immune response. This process appears to occur at least 6 months prior to any atypical appearance of the transforming cell. The transformation which can be demonstrated in normal appearing cells adjacent to a malignant lesion appears to suggest that the transformation process is not defined by a mutation in one altered cell, but rather occurs within a field within which the tumor process had been initiated. This field appears to represent a large cluster of transformed cells existing in a dormant state induced by the presence of the tumor that had progressed within the field itself. Removal of the developing malignancy appears to remove any localized immune suppressive activity which allows further transformation within those cells already existing within the field. As the tumor progresses genetically it initiates the production of a number of factors including matrix metalloproteinase. This allows the cell to invade adjacent vessels that have grown into the tumor but also results in the break down of e-cadherin to its small form the s-e cadherin which then initiates progression and metastasis. Many tumors that 'metastasize' or spread throughout the body reside in that specific location of implantation as a result of the surface glycoprotein expressed on the outer cell membrane of the tumor, a seed and soil concept. As such, that lesion metastatic to liver can only grow in the liver parenchyma and can not spread to other organs. At best, the lesion can only proliferate in that organ in which it has implanted. Because of the extremely low level of oncofetal protein expression within any tumor system, the host immune system virtually bypasses this antigen allowing uninterrupted growth of the tumor within the host. At best, host immunity can only initiate a process of tumor surveillance wherein the host can identify and destroy one or two criminal cells in a population of thousands of such cells. Prehn had originally suggested that in order to induce immune recognition, one must pool the tumor immunogen to its threshhold level of activity to assure specificity in recognizing the system. The important antigens defining an array of malignant lesions expressed in the colorectal system was defined by Hollinhead employing pooled allogeneic membrane protein. This pooled material was subfractioned by sephadex gel and discontinuos polyacrilamide gel electrophoresis. The components of the separation process were tested by delayed cutaneous skin hypersensitivity in patients with the specific tumor, patients with different malignancies and normal volunteers. For colon cancer, an antigen of approximately 60-80 kd was defined. Testing for an immune response, doses of approximately 500-1000 ugm of partially purified antigen were found necessary to turn on effective immune reactivity. . FDA suspected that even though the final antigen preparations represented a single band on isoelectrophoresis that the protein composition was complex and probably represented several antigens or oncofetal proteins migrating to the same region on the gel. As such, it was suggested that a genetically engineered preparation would be required for future clinical trials eliminating the process of producing a pooled allogeneic preparation. As such, by todays standard, this form of preparation using pooled tumor from operative specimens would be subject to the potential of possible contamination by HIV, HPV or Hep B and C. Monoclonals were therefore developed to the antigen used in the study and obviously as anticipated several mAbs were obtained that cross reacted with colon cancer. The mAbs in the IgG1 format were found capable of destroying tumor by ADCC and valuable in the purification of antigen in anticipation of mass spectroscopy studies. To clarify the antigen composition, HPLC was performed with at least 3 significant bands being defined in the colorectal/pancreas oncofetal proteins . Three distinct antigens have been isolated, characterized and developed for clinical trials. The pooled allogeneic antigen when first employed , was able to produce between 70 and 90 % survival free of disease recurrence. While the antibodies derived from these proteins are being employed with significant responses in those patients having failed all therapeutic modalities , vaccines are now being developed GMP to use in those patients where post surgery, there is a very high rate of recurrence at the 1-2 year post surgical period of time. An example is in found in those patients undergoing pancreatectomy where even when nodal disease may be absent, at 1-2 years post surgery, 90% of the patients will present with recurrent disease.

Time:

Title: Transmission-blocking vaccines for arbovirus infection

Tonya Colpitts
Carolina School of Medicine, USA

Biography

Dr. Colpitts is a molecular virologist primarily interested in flavivirus research with over 15 years experience in the laboratory. Her graduate research at the University of Texas Medical Branch included developing and adapting several mammalian assays to function in mosquito cells and her dissertation work explored many aspects of virus-mosquito protein interactions. She demonstrated that the cellular endocytic machinery is highly evolutionarily conserved between mosquitoes and mammals, and that alphaviruses require functional endocytosis for entry into both cell types. In her postdoctoral research at Yale University School of Medicine, Dr. Colpitts developed a tandem affinity purification (TAP) assay for use in insect cells and discovered many previously unknown mosquito proteins that interact with both structural and non-structural flavivirus proteins. She went on to show that these proteins are important for productive infection. Currently, Dr. Colpitts is an Assistant Professor at the USC School of Medicine. Dr. Colpitts has also designed and performed microarray analysis to get a global picture of alterations in gene expression during flavivirus infection in the Aedes aegypti mosquito. Using this data, she identified a number of significantly altered genes and identified corresponding proteins that inhibit dengue, Yellow Fever and West Nile virus infection in cells, live mosquitoes and mice. She recently published on the use of one of these proteins, CRVP379, as a putative dengue virus transmission-blocking vaccine (TBV) and another as an inhibitory factor during dengue infection in mammals (D7).

Abstract

Infectious diseases caused by arboviruses (viruses transmitted by arthropods) are undergoing unprecedented epidemicactivity and geographic expansion. With the recent introduction of West Nile virus (1999), chikungunya virus (2013) andZika virus (2015) to the Americas, stopping or even preventing the expansion of viruses into susceptible populations isan increasing concern. With a few exceptions, available vaccines protecting against arboviral infections are nonexistentand current disease prevention relies on vector control interventions. However, due to the emergence of and rapidlyspreading insecticide resistance, different disease control methods are needed. A feasible method of reducingemerging tropical diseases is the implementation of vaccines that prevent or decrease viral infection in the vector.These vaccines are designated ‘transmission blocking vaccines’, or TBVs. Here, we will discuss the current state of arbovirus vaccine development, summarize TBV research, present several promising TBV candidates and the potential for successful prevention of arbovirosis using TBVs. We will also present data from our research experiments testing an Aedes protein, CRVP379, as a putative TBV for dengue virus infection

Time:

Title: Design and improve foot-and-mouth disease vaccine properties by reverse genetic system

Keshan Zhang
Chinese Academy of Agricultural Science, China

Biography

Keshan Zhang received his bachelor degree in animal medicine (2003) from Henan Agricultural University, obtained his Ph.D degree in preventive veterinary medicine(2008) from Huazhong Agricultural University. As a postdoctor in China animal disease control center(2011-2013) , and a visiting scholar in Tufts Cummings School of Veterinary Medicine in MA USA(2013-2014). His research interest focus on the inflammatory signal pathways related to FMDV infection and FMD vaccine development. In recent 5 years, four monographs have been published,more than 60 scientific papers published, 13 of them were SCI papers ( as first author or co-first author) which published in Plose one, Virus genes, Vector-borne and Zoonotic diseases, and Virology journal et al. 6 patents were applied, 4 of them have been authorized.

Abstract

Foot-and-mouth disease (FMD) is a contagious disease of cloven-hoofed animals, it leads to enormous economic loss worldwide. One of the most important measures to control and prevent FMD is the whole-virus inactivated vaccines. Virus isolation from field and acclimation are the traditional methods to get virus seeds for FMDV vaccine, but it is very difficult and time wasting to select proper virus seeds for vaccine production. To solve the above problems and enhance FMD vaccine properties, An efficient viral recovery system based on RNA polymeraseI was developed, it’s an efficient tool that one plasmid express infective FMDV. There were many topologies within one FMDV serotype, only very low cross protection among them.In order to broaden antigen spectrum for FMD vaccine serotypeO, we construct recombinant virus(Re-O/wide spectrum )which contains antigen site 4( from Cathay topotye), site 2 (from PanAsia1), site 3(from PanAsia1) and site1+5(from SEA).Vaccine made of Re-O/wide spectrum virus can provide complete protection under the challenge of FMDV from topotye of Cathay,PanAsia1 and SEA. FMD serotype A (A/WH/CHA/09)was outbroken in China 2009, but TCID50 of the virus isolated from field was very low, it can’t be used as the seed of vaccine production. Results of sequence analysis indicated that mutants of SL structure in 3’UTR happened. Previous researched showed that SL play crucial role in the growth of FMDV and mutated SL lead to low replication in vivo and vitro. Based on previous researches, to increase growth properties SL reverse mutation virus(Re-A/WH/CHA/09) was constructed. Growth properties showed TCID50 of Re- A/WH/CHA/09 was higher than wild type A/WH/CHA/09, it changed from 107.5 to 104.3. Vaccine made of Re- A/WH/CHA/09 virus can provide complete protection with A/WH/CHA/09FMDV challenge. On the basis of above results, conclusions can be made that reverse genetic technology was a powerful tool for FMD vaccine design and improvement.

Time:

Title: A novel N-glycosylation mutated HCV E2 DNA Vaccine and its monoclonal neutralizing antibody provide a vigorous and full protecive immune response against HCV infection in vivo

Xiaolian Zhang
Wuhan University, China

Biography

Dr. Xiao-Lian Zhang received her PhD in 1997 from the Hong Kong University of Science and Technology, and had her post-doctoral fellowship during 1997-2001 at University of Maryland, College Park, Maryland, USA. She served as Research Specialist at University of Maryland, College Park, Maryland, USA during February 2001-August 2001. In September 2001, Dr. Xiao-Lian Zhang joined Wuhan University School of Medicine (Wuhan, China) as a full-professor, where, since 2014 served as the Head of the Department of Immunology. She also served as a professor at State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, and Medical Research Institute.Dr. Xiao-Lian Zhang’s main research interests include pathogenic microorganism infection and immunity. She has more than 90 published articles in SCI, and authored several books and book chapters on infectious disease immunology related topics.

Abstract

Background: Approximately 2.35% of the world’s population is chronically infected with hepatitis C virus (HCV) and eventally with risking of progression to cirrhosis and hepatocellular carcinoma. Current therapy is only partially effective and the development of an effective vaccine of HCV remains a high priority goal. The heavily glycosylated viral envelope glycoproetin E2 is a candidate vaccine antigen. A genetically-engineered, inbred mouse model with inheritable susceptibility to HCV would be ideal for studying HCV vaccine candidate. Results: In this study, using a DNA prime-protein boost immunization strategy, we found that a secreted E2(sE2)-N2, with specific N-glycosylation deletion could enhance the highest cellular immune response compared to the WT E2 and other N-glycosylation mutants.The sE2-N2 antiserum efficiently neutralized the infection of cell cultured HCV (HCVcc, genotype 2a) and HCV pseudo particles (HCVpp, genotypes 1 to 7) to Huh7.5.1. Additionally, sE2-N2 enhanced the interleukin-12 (IL-12) production and antigen-presenting activity of CD11c+ dendritic cells (DCs) by inducing CD4+Th1 polization and the production of perforin and granzyme B (GrB) in CD8+T cells. More importantly, sE2-N2 DNA immunization and the selected anti-E2 mAb 1C1 from sE2-N2 immunized mice effectively neutralized HCVcc infection in the genetically humanized mice. Conclusion: As our knowledge, this is the first report about HCV Vaccine and its monoclonal neutralizing antibody provide a vigorous and full protecive immune response against HCV infection in vivo. The current study may offer a promising strategy for the development of effective B- and T-cell-based HCV vaccine, and meanwhile highlights the role of envelope protein glycosylation in viral immune evasion.

Time:

Title: Chimpanzee adenovirus vector-based avian influenza vaccine completely protects mice against lethal challenge

Dongming Zhou
Chinese Academy of Sciences, China

Biography

Dr. Dongming Zhou is a professor and the head of Anti-infection Immunity and Vaccine Research Unit at Institute Pasteur of Shanghai, Chinese Academy of Sciences. His research interest is to generate noveladenovirus as gene transfer vehicles, and to establish platformsfor vaccine development or molecular therapy based on recombinant adenovirus, andto explore the mechanisms involved in novel vaccines or gene therapy methods. Dr. Zhou received his M.D. from Suzhou Medical College in 1993, and his M.P.H. from Hunan Medical University in 1998, and his Ph.D. from Central South University in 2001. He completed his postdoc training in immunology at the Wistar Institute in2006, and then worked as a staff scientist at the Wistar Institute in the period of 2006 to 2011.He has published over 30 peer-review articles and applied 10 US and Chinese patents.

Abstract

Highly pathogenic avian influenzaviruses such as H5N1, H7N9, may give rise to the next influenza pandemic due to the reassortment and mutation of theirgenomes. The clinical use of seasonal influenza vaccinesincludes inactivated influenza vaccine and live attenuated influenza vaccine cannot protect the human from the heterogenous influenza viruses infection, such as the avian origined influenza viruses. Thus the development of avian influenza vaccineis in critical demands. Chimpanzee adenovirus (Ad) vectors are a novel type of vaccine carriers that share the advantages of human serotype Ad vectors but without being affected by pre-existing human neutralizing antibody to the vaccine vector, and have been considered as promising vaccine vectors due to their high immunogenicity, broad cell tropism, high gene expression, good genetic stability, etc.Various vaccine candidates based on chimpanzee Ad vectors have been developed for infectious diseases and cancers. Based on replication-deficient chimpanzee Ad vectors, AdC7 and AdC68, we generated two novel vaccine candidates for H5N1 and H7N9, termed as AdC7-H5HA and AdC68-H7HA,which expressing H5N1Hemagglutinin (HA) and H7N9 HA, respectively. After tested in mice, both vaccine candidatessignificantly reduced the virus loads and pathological lesions in the lung tissues, and conferred complete protections against lethal challenge by homologous viruses. Mechanistically, both AdC7-H5HA and AdC68-H7HA induced HA-specific humoral and cell-mediated immune responses in mice. Sera transfer experiment and T cell depletion experiment demonstrated that neutralizing antibodies as well as HA-specific CD8+ T cell responses play important roles in protection. In conclusion, our study suggests that chimpanzee Ad vector expressing influenza virus HA may represent a promising vaccine candidate for avian influenza viruses and other influenzavirus subtypes.

Keynote Speaker

Time:

Title: Towards a systems biology understanding of Type-2 Immune initiation

Justine T. Tigno-Aranjuez
UCF College of Medicine, USA

Biography

Dr. Justine Tigno-Aranjuez received her B.S. in Molecular Biology and Biotechnology from the University of the Philippines. She received her PhD. in Pathology from Case Western Reserve University studying the role of adjuvants in shaping T cell responses. She continued at Case Western as a Postdoctoral Fellow and Instructor doing research on the posttranslational control of signaling mediated through the bacterial peptidoglycan sensor NOD2. She is currently an Assistant Professor at the University of Central Florida and continues to study innate immune signaling pathways in inflammatory diseases. She has published in journals such as Genes & Development, Molecular and Cellular Biology, Cell Reports, The Journal of Immunology, and the Journal of Biological Chemistry. While at Case Western University, she also filed 2 patents in which she was 50% co-inventor. She has been the recipient of an American Cancer Society Postdoctoral Fellowship, an NIDDK NRSA F32 award, and is currently NHLBI K99/R00 recipient.

Abstract

Type 2 immune stimuli are unique. Unlike Th1 or Th17 stimuli which rely heavily on pattern recognition, type 2 agonists share very little in common with each other. Despite this, diverse type 2 stimuli are able to promote very similar downstream adaptive immune responses. This knowledge has, in turn, led to the development of therapeutic approaches which, for the most part, target the symptoms but do not modify the course of type 2 inflammatory diseases. This then raises the questions, “What do we currently understand about the rules governing type 2 immune initiation?” and “Are we currently using the right tools to enable us to come to a unified view of how our innate immune system recognizes and responds to type 2 agonists?” This presentation will give an overview on what is currently known about innate immune recognition of type 2 stimuli, the approaches that can be used to develop a type 2 innate immune signature, and the potential therapeutic applications of such a strategy.

Keynote Speaker

Time:

Title: Analysis of viral quasispecies for vaccine characterization

Juan Carlos Zapata
University of Maryland,USA

Biography

My main research interest is in virus-host interactions using animal models, genomic profiling, and basic molecular virology. It is focused not only on host responses but also on changes that occur in the viral population in order to describe virus-host coevolution. During the characterization of the Lassa vaccine candidate ML29, I identified mutations in the arena virus nucleo capsid protein (NP) that are likely to impact viral pathogenesis and the induction of protective immunity. Additionally, I am involved in a new line of work focusing on retroviral latency. Under Dr. F. Romerio leadership I am working in detecting and characterizing viral factors related with HIV latency in the reservoir cells and with Dr. Y. Tagaya I am implanting patient-derived ATL cells into NSG mice to study cancer pathogenesis, treatment options, and vaccine development against HTLV-1.

Abstract

When referring to a virus strain we are describing the most abundant variant from a closely-related virus swarm containing individual particles with broadly-distributed mutations. A viral isolate containing many variants, called quasi-species, could act as a unit of selection through a continuous dynamic process of genetic variation, competition, and selection. However, it is important to emphasize that the whole “virus swarm” contributes to the characteristics of the virus strain and will be the target of selection instead of individual variants. For example, some variants carrying lethal mutations not only compete with the fittest replicating unit but also cooperate with other mutants complementing each other, thus assuring the survival of the units containing "lethal mutations". Several studies describe the effect of the mutant spectra in the virus population phenotype making it more virulent or more attenuated according to the predominant quasi-species. For example, defective interfering particles could play a role in attenuating the virulence of a viral swarm by interfering with virus replication. In the case of live vaccines, the final goal is to select one population with attenuated phenotype (low pathogenicity) and high genomic stability (increased fidelity of replication). Ensuring that the viral population, contained in the preparation, does not have the capacity to adapt to new conditions in the host due to low quasi-species diversity but replicating enough to induce protection. Thus, changes in virus diversity, can affect virus fitness and viral tropism and produce a spectrum of unexpected outcomes after vaccination depending on particular conditions of the virus-host interaction. With the new sequencing tools, it is easy to characterize viral populations, in this case in vaccine preparation, which allows controlling the proportion of each viral-quasispecies. This talk will be focused on the use of the study of viral populations for vaccine characterization using as a model a Lassa vaccine candidate.

Sessions:
HIV/AIDS Vaccines & Clinical Trails
Human Vaccines – Infectious & Non Infectious Diseases & Immunology/Animal models

Time:

Title: The contribution of immune-based therapy towards functional HIV cure

Maja A. Sommerfelt
Bionor Pharma ASA, Norway

Biography

Maja A. Sommerfelt is Director of Research and External Innovation at Bionor Pharma ASA. She obtained her PhD degree from the University of London, United Kingdom, at the Institute of Cancer Research where she studied receptors for diverse retroviruses on human cells. She carried out post-doctoral research at the University of Alabama at Birmingham in the United States where she studied retroviral assembly using molecular techniques. She then joined the University of Bergen in Norway where she became Professor in 1996. Maja Sommerfelt joined Bionor Pharma ASA in 2002 and has been involved in clinical research and development of the company’s lead product, Vacc-4x.

Abstract

HIV infection remains a formidable global health threat with 37 million adults and children living with HIV. Combination antiretroviral therapy (ART) has made a significant impact on HIV morbidity and mortality, but is unable to cure HIV infection due to the reservoir of latently infected cells, particularly long-lived immune memory cells. ART must therefore be taken for life. The HIV ‘Shock and Kill’ concept involves latency reversal in the presence of ART to reactivate (shock) latent reservoirs that can then be killed by the lytic effects of the virus, or the immune system. However, it transpires that latency reversal alone is insufficient to reduce HIV reservoirs. The REDUC study (NCT02092116), sponsored by Bionor Pharma ASA, was the first to include therapeutic vaccination inthe HIV ‘Shock and Kill’ concept. REDUCwas carried out in two parts at Aarhus University Hospital, Denmark. Part A (n=6) tested the effects of a single cycle of 3 romidepsin intravenous (iv) infusions during ART, to confirm safety and the capacity for latency reversal. In Part B (n=20), participants were immunised with the peptide-based therapeutic vaccine, Vacc-4x (1.2mg) administered as 4 weekly intradermal (id) injections followed by 2 weekly booster injections 8 weeks post priming. Recombinant human granulocyte macrophage colony stimulating factor (rhuGM-CSF) administered id was used as a local adjuvant. Three weeks post-immunization, participants received one cycle of romidepsin infusions and nine weeks later, eligible partcipants underwent a monitored antiretroviral pause (MAP). ART was resumed when plasma viral load reached 1000copies/mL. In part A, 5/6 participants showed detectable plasma HIV RNA during latency reversal, but HIV reservoirs (total HIV DNA)remained unchanged. In Part B, in 9/17 participants, there was no detectable plasma HIV RNA at any time-point during the latency reversal period. For the remaining participants, low level virus load was detected after either one or two of the romidepsin infusions. There was a statistically significant reduction of total HIV DNA (39.7%; p=0.012; n=16). Analysis of integrated DNA showed a reduction that was not statistically significant (19.2% p=0.123; n=15). A viral outgrowth assayto measure replication competent virusin part B showed a reduction that was statistically significant (38%; p=0.019; n=6). However, the reduction in HIV reservoirs was not sufficient to delay the time to viral rebound on treatment interruption. These findings support the inclusion of immune-based therapiestowards functional HIV cure, and other clinical studies involving therapeutic vaccination are in progress.

Time:
12:05 -12:30

Title: Feasibility of Monitoring Cell Mediated Immunity during Vaccine Trials

Magdalena Tary-Lehmann
Cellular Technology Limited (CTL), USA

Biography

Dr. Magdalena Tary-Lehmann is Co-Founding Scientist and Chief Scientific Officer for Cellular Technology Limited (CTL). Dr. Tary-Lehmann received her M.D. and Ph.D., both from the University of Tübingen, Germany. Her postdoctoral training in Immunology was at the University of California, Los Angeles. She moved thereafter to Case Western Reserve University, where she was awarded tenure and appointed as Associate Professor in the Department of Pathology. As Chief Scientific Officer for CTL she oversees the performance of immunology assays in CTL’s GLP- and CLIA compliant contract laboratory for various pharmaceutical and biotechnology clients.

Abstract

Despite the technical advances that facilitated many of the remarkable insights into human immunology in basic research settings, the primary challenge for pharmaceutical, clinical and regulatory entities has been the translation of the gained theoretical knowledge into useful, practical tools that produce reliable, clinically relevant information in large trials while being economically feasible. The ultimate goal is to enable the prediction of outcomes based on biomarkers and other immune monitoring data in order to develop strategies for successful intervention with vaccines and therapeutics. I will discuss the need for early considerations to the standardization of specimen processing, cryopreservation, sample management and assay systems that are vital steps for the successful design and execution of pre-clinical and clinical trials for Vaccinesthat deliver consistent and regulatory acceptable immune monitoring data. Measurements of antibodies in bodily fluids (e.g., by ELISA) have provided robust and reproducible results for decades, and such assays have been validated for monitoring of B-cell immunity. In contrast, measuring T-cell immunity has proven to be more of a challenge, due to the need to test live cells in functional assays ex vivo. While T cells play a critical role, reliable measurements of antigen-specific T cell responses ex-vivo remain seemingly problematic, as typically, T cells occur in very low frequencies in test samples, such as peripheral blood. Therefore, monitoring antigen-specific T cells and their effector functions is critical for the understanding of diseases, and for proper assessments of the efficacies of specific vaccine therapies. In addition, for an assay to reliably measure T-cell function(s), it needs to be warranted that the test conditions are such that the function of T cells in vitro remains unimpaired relative to ex vivo. In theory, several techniques are available, including the use of HLA/peptide tetramers, intra-cellular cytokine staining, ELISA and ELISPOT. In praxis, however, only ELISPOT assays might meet this need, because of the requirement for: (i) very high sensitivity to detect the rare antigen specific T cells, (ii) the limited number of cells obtainable from patients, (iii) the assay’s independence of the HLA genotype of the test subjects, and (iv) the ease of performing the assay. Examples of such successful T cell monitoring will be presented.

Time:

Title: Analysis of viral quasispecies as quality control of live vaccines-e.g. Lassa vaccine candidate, ML29.

Juan Carlos Zapata
University of Maryland, USA

Biography

My main research interest is in virus-host interactions using animal models, genomic profiling, and basic molecular virology. It is focused not only on host responses but also on changes that occur in the viral population in order to describe virus-host coevolution. During the characterization of the Lassa vaccine candidate ML29, I identified mutations in the arena virus nucleo capsid protein (NP) that are likely to impact viral pathogenesis and the induction of protective immunity. Additionally, I am involved in a new line of work focusing on retroviral latency. Under Dr. F. Romerio leadership I am working in detecting and characterizing viral factors related with HIV latency in the reservoir cells and with Dr. Y. Tagaya I am implanting patient-derived ATL cells into NSG mice to study cancer pathogenesis, treatment options, and vaccine development against HTLV-1.

Abstract

When referring to a virus strain we are describing the most abundant variant from a closely-related virus swarm containing individual particles with broadly-distributed mutations. A viral isolate containing many variants, called quasi-species, could act as a unit of selection through a continuous dynamic process of genetic variation, competition, and selection. However, it is important to emphasize that the whole “virus swarm” contributes to the characteristics of the virus strain and will be the target of selection instead of individual variants. For example, some variants carrying lethal mutations not only compete with the fittest replicating unit but also cooperate with other mutants complementing each other, thus assuring the survival of the units containing "lethal mutations". Several studies describe the effect of the mutant spectra in the virus population phenotype making it more virulent or more attenuated according to the predominant quasi-species. For example, defective interfering particles could play a role in attenuating the virulence of a viral swarm by interfering with virus replication. In the case of live vaccines, the final goal is to select one population with attenuated phenotype (low pathogenicity) and high genomic stability (increased fidelity of replication). Ensuring that the viral population, contained in the preparation, does not have the capacity to adapt to new conditions in the host due to low quasi-species diversity but replicating enough to induce protection. Thus, changes in virus diversity, can affect virus fitness and viral tropism and produce a spectrum of unexpected outcomes after vaccination depending on particular conditions of the virus-host interaction. With the new sequencing tools, it is easy to characterize viral populations, in this case in vaccine preparation, which allows controlling the proportion of each viral-quasispecies. This talk will be focused on the use of the study of viral populations for vaccine characterization using as a model a Lassa vaccine candidate.

Time:

Title: Assessing the non-fatal burden of childhood Diarrhea Including malnutrition, physical growth, and cognitive Development

Ibrahim Abdel-Messih Khalil
University of Washington, USA

Biography

Ibrahim had his medical training and training in Clinical Pediatrics at Cairo University. He has clinical experience at the Embaba Fever Hospital, the major infectious diseases hospital in Egypt where he was managing the Diarrheal diseases department. He started his medical research career after joining the staff of the U.S. Navy Medical Research Unit (NAMRU-3) in Cairo where, as a Clinical Epidemiologist, he participated in a number of enteric disease and diarrhea vaccine studies and co-directed the U.S. Military Tropical Medicine Course. During his twelve years at NAMRU-3, Ibrahim also served as a co-chair of the Institutional review Board (IRB). Ibrahim also participated in many Outbreak Investigations through the collaboration of US NAMRU-3 and the Egyptian Ministry of Health. Ibrahim has also served as a consultant to the WHO Enterics Program. In 2008, Ibrahim joined Novartis Vaccines and Diagnostics in Siena, Italy, then he joined the Faculty of University of Washington, at the Institute For Health Metrics and Evaluation (IHME).

Abstract

The global burden of childhood diarrhea is substantial, but a tremendous decline has occurred in the last several decades, but the morbidity impact of diarrheal diseases and enteric infections, especially in early childhood, remains a concern. The Global Burden of Disease Study (GBD), a systematic, scientific effort to quantify the comparative magnitude of health loss by age, sex, and population over time, quantifies diseases using disability adjusted life years (DALYs) lost where DALYs are the sum of mortality and morbidity. Traditionally, the DALYs from diarrhea have been dominated by childhood deaths, but this may underestimate the full picture of diarrhea DALYs. We have conducted a systematic review of published and unpublished data and performed separate meta-analyses of the impact of childhood diarrhea on physical growth and on cognitive development. Our results show that days of diarrhea significantly increase the risk of long term effects, like subsequent physical growth stunting. Each day of diarrhea is associated with a decrease in height-for-age z-score of 0.003 and with weight-for-age z-score of 0.006. Further, physical growth is significantly associated with cognitive development as each unit increase in height-for-age z-score increases standardized intelligence scores by 0.08. However, diarrhea is not significantly associated with cognitive development in our analysis suggesting that malnutrition may be a modifier in this relationship. Our findings call for including long-term sequelae in GBD and other analyses and better quantifying the non-fatal consequences of childhood diarrhea for a more complete understanding of the burden of diarrhea. Lifelong impairment of cognition and lack of physical development due to diarrheal diseases may be greater than previously estimated by GBD. Our research also calls for the acceleration of effective programs to prevent diarrheal diseases and enteric infections in developing countries to secure a healthy and productive life for future generations.

Time:

Title: An Epstein-Barr virus gp350 subunit vaccine that targets the virus neutralization site

Carolina Alfieri
University of Montreal, Canada

Biography

Dr Carolina Alfieri is a research virologist at the Sainte-Justine University Hospital Centre and associate professor with the Department of Microbiology, Infectiology and Immunology at the University of Montreal. Much of her research and publications have focused on transplant virology, with an emphasis on both mechanistic and translational aspectsof Epstein-Barr virus pathogenesis in immunocompromised patients. Dr Alfieri’s laboratory is currently working on the development of a subunit vaccine to confer protection against infectious mononucleosis and cancers linked to infection by the Epstein-Barr virus. This work is supported by the Canadian Institutes for Health Research and the Cancer Research Society.

Abstract

The Epstein-Barr virus (EBV) is the etiologic agent of infectious mononucleosis andan important cofactor in nasopharyngeal carcinoma,various T and B cell lymphomas and several epithelial cancers. The major virion surface glycoprotein (gp)350is viewed as the best vaccine candidate to prevent infectious mononucleosis and EBV-associatedcancers because natural antibodies to gp350 block virus infection and effectively neutralize the virus. Our laboratory has identified peptide sequences on the gp350 molecule that arerecognized by a virus neutralizing monoclonal. These peptides were shown to generate production of virus-blocking antibodies upon injection in mice.In our recent follow-up work, we postulatedthat a vaccine constructwhich correctly presents these peptides candirect the immune system to generate higher levels of protective antibody as compared to presentation of the entire gp350 molecule. To test this hypothesis, we used a prime-boost strategy wherein mice were primed with recombinantfull-length gp350 (907 amino acid sequence) andboosted with a truncated form of the gp350 molecule encompassingthe gp350 peptides identified in our earlier work. Results indicate thatboosting with the smaller gp350 construct produced higher concentrations of neutralizing antibodies when compared to boosting with the entire gp350 molecule.These datasuggest that a vaccination strategy which enablesthe immune system to focus on the virus neutralizing epitopecan generate a more robust and effective antibody response, which translates to better protection against EBV infection.

Time:

Title: Vaccine-induced CD4+Ox40+ T cells are heterogeneous and highly protective against Mycobacterium tuberculosis in mice

Steven Derrick
FDA, USA

Biography

Steven Derrick has been working for the Food and Drug Administration for 16 years conducting tuberculosis vaccine research. His main research interests include T cell mediated immune responses with the objective to discover correlates of immunity to TB with the ultimate goal of developing a better TB vaccine. He is currently serving on the editorial board for Clinical and Vaccine Immunology and has published over 40 papers related to infectious diseases. In addition to his TB vaccine research, Steven also conducts regulatory reviews including Investigational New Drug applications submitted to the FDA.

Abstract

Protective immune responses against tuberculosis are not completely understood, and although it has been established that T cells, and cytokines, such as IFN-γ and TFN-α, are necessary, the full picture of what constitutes a protective immune response remains ill-defined. This paper describes a population of CD4+Ox40+ (CD134) T cells that exhibit both high side scatter (SSC) and forward scatter (FSC) when analyzed by flow cytometry and were highly protective. When splenocytes from mice immunized with BCG formulated in dimethyl dioctadecyl ammonium bromide (DDA) and D(+) trehalose 6,6 dibehenate (TDB) (DDA/TDB) adjuvant (BCG/Adj) were stimulated with BCG ex vivo followed by enrichment of CD4+Ox40+ T cells, adoptive transfer into mice conferred significant protection against an aerosol infection with Mycobacterium tuberculosis relative to nonimmunized control mice. When as few as 105 cells were transferred, a 0.7 log10 CFU reduction was observedw one month post-aerosol challenge, and following transfer of 106 cells, a 1.3 log10 CFU reduction was detected. In contrast, CD8+Ox40+ and CD4+Ox40 negative (CD4+Ox40neg) T cells were not found to be protective. Further characterization of CD4+Ox40+ T cells revealed that subpopulations of these cells expressed CD69, CD25, PD-1, BCL-6, T-bet, RoRγt and/or CXCR5 and secreted multiple cytokines (IFN-γ, TNF-α, and IL-2) indicating that these cells represent a highly protective, yet heterogenous T cell population. Expression of these markers and cytokines in CD4+Ox40neg T cells was significantly and considerably lower. These data suggest that induction of CD4+Ox40+ T cells should be targeted when designing new vaccines against M. tuberculosis.

Time:

Title: The Dual Role of RIP2 Kinase in a murine model of dermatophagoides farinae asthma

Justine T. Tigno-Aranjuez1
UCF College of Medicine, USA

Biography

Dr. Justine Tigno-Aranjuez received her B.S. in Molecular Biology and Biotechnology from the University of the Philippines. She received her PhD. in Pathology from Case Western Reserve University studying the role of adjuvants in shaping T cell responses. She continued at Case Western as a Postdoctoral Fellow and Instructor doing research on the posttranslational control of signaling mediated through the bacterial peptidoglycan sensor NOD2. She is currently an Assistant Professor at the University of Central Florida and continues to study innate immune signaling pathways in inflammatory diseases. She has published in journals such as Genes & Development, Molecular and Cellular Biology, Cell Reports, The Journal of Immunology, and the Journal of Biological Chemistry. While at Case Western University, she also filed 2 patents in which she was 50% co-inventor. She has been the recipient of an American Cancer Society Postdoctoral Fellowship, an NIDDK NRSA F32 award, and is currently NHLBI K99/R00 recipient.

Abstract

Allergens are comprised of a heterogeneous group of substances, which, despite being structurally and functionally diverse, can elicit very similar downstream type 2 adaptive immune responses. How this is accomplished is not completely understood. Elucidating the innate immune mechanisms involved in responding to these disparate stimuli may help guide the development of vaccines or therapies for type 2 disorders. One of the few innate immune receptors that have been reported to elicit type 2 adaptive immune responses is the peptidoglycan sensor NOD2. In this study, we examine the role played by the effector kinase RIP2, which mediates signaling downstream of the NOD2 receptor. Using an in vitro culture model of primary murine tracheal epithelial cells and in vivo model of Dermatophagoides farinae mediated allergic airway inflammation in combination with WT or RIP2 KO mice, we find that RIP2 plays dual roles in both regulating and contributing to allergic airway disease. We show that in airway epithelial cells, RIP2 is tyrosine phosphorylated in response to exposure with extracts of Dermatophagoides farinae. Loss of RIP2 results in a reduction in inflammatory chemokine and cytokine production upon stimulation with low doses of D. farinae but an exaggerated response upon stimulation with higher doses of allergen. Using the D. farinae asthma model, we demonstrate that loss of RIP2 leads to a reduction in lymphocyte and eosinophil recruitment, but results in increased airway hyperresponsiveness in response to challenge with methacholine. These data illustrate the complexity of studying innate immune signaling pathways in a type 2 mediated disease such as asthma and cautions the use of inhibitors of RIP2 kinase for such disorders.

Sessions:
Poster Presentations

Time:

Title: One Shot Nipah Virus like Particle (NiVVLP) Vaccine study

Micah Tepora
University of Hawaii, USA

Biography

Miacah ptepora has B.S. in Biological Sciences from Loyola University. Her research interest is infectious diseases. She has completed her M.S. Tropical Medicine from University of Hawai’i at Manoa.

Abstract

Nipah virus (NiV) a highly lethal zoonotic paramyxovirus that was first recognized in Malaysia in 1998. Fruit bats (Pteropusspp) are the reservoir host of this virus. NiV infection caused a severe febrile encephalitis outbreak in humans who worked in close contact with pigs suffering from respiratory disease. The case fatality rate in humans was around 40%. Since 2001, the virus has re-emerged in Bangladesh and India where bats have been identified as the principal source of the virus and the case fatality ~60-100%. In this study, we have produced mammalian cell-derived native Nipah virus-like particles (NiV VLPs) composed of NiV G, F and M proteins. We have done a One Shot vaccine study at NIAID IRF facility. In vitro studies using transmission electron microscopy (TEM), the VLPs were structurally similar to authentic virus, functionally assembled and immuno-reactive. Western blot analysis showed that indeed the VLPs were composed of the G, F and M proteins. Hamsters vaccinated with adjuvantedNiV VLP survived

Time:

Title: Safety and protective efficacy of respiratory syncytial virus-like particles in a murine model

Micah Tepora
University of Hawaii, USA

Biography

Miacah ptepora has B.S. in Biological Sciences from Loyola University. Her research interest is infectious diseases. She has completed her M.S. Tropical Medicine from University of Hawai’i at Manoa.

Abstract

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infections in children worldwide, particularly bronchiolitis and pneumonia. Most children be infected with RSV by the time they reach the age of 2, with incidence rates higher during early months of infancy. It is estimated that in the United States, an average of about 58,000 children under the age of 5 are hospitalized due to RSV each year. To this day, there is still no licensed vaccine. In this study, we evaluated the safety and efficacy of monophosphoryl lipid A (MPLA)-adjuvanted RSV virus-like particles (RSV VLPs) that express the F and G surface proteins and the M matrix protein, in a murine model. F is a crucial protein in RSV vaccine development because it contains neutralizing epitopes that can be targeted by neutralizing antibodies. We conducted an in vivo analysis by immunizing BALB/c mice with diluent, RSV, MPLA-adjuvanted RSV VLPs, or non-adjuvanted RSV VLPs. Our results indicated that two intramuscular immunizations of the MPLA-adjuvanted RSV VLPs elicited a strong neutralizing antibody response. It also showed that immunization induced a RSV-specific IgG response and higher IgG2a levels compared to IgG1 which suggested a Th1-biased response. MPLA-adjuvanted RSV VLPs were also able to protect mice from RSV infection in the upper and lower respiratory tracts and the development of disease in the lungs based on the histopathology of the lungs. Our findings thus far lead us to conclude that using MPLA-adjuvanted RSV VLPs is a promising candidate for a RSV vaccine.

Time:

Title: Virus like particle vaccine expressing immune-modulating molecules

Jae Min Song
Sungshin University, South korea

Biography

Abstract

Virus-like particle (VLP) technology is an attractive platform for seasonal and pandemic influenza vaccine development. We showed that influenza VLPs can be modified using immune-modulating molecules such as GM-CSF to enhance VLP immunogenicity. For this study, chimeric VLPs were incorporated with GM-CSF, to enhance anti-influenza immunogenicity. Our results indicate that immunizations with the chimeric HA/GM-CSF VLPs elicited more potent and broadly neutralizing antibodies and neuraminidase-inhibiting antibodies in sera, and induced higher numbers of hemagglutinin-specific antibody-secreting cells and germinal center B cell subsets in splenoctyes. Immunization with the chimeric HA/GM-CSF VLPs induced stronger Th1 and Th2 cellular responses. The chimeric HA/GM-CSF VLPs showed heterlologous protective immunity. It is our hope that these findings provide useful information for developing multi-subtype influenza vaccines. Keywords: Virus-like particle; immune-modulating molecules; vaccine

Time:

Title: Development of a Tissue culture origin vaccine for infectious laryngotracheitis virus

Eun-Jung Choi
Konkuk University, Korea

Biography

Ms.Choiis a postgraduate student at College of Veterinary Medicine, Konkuk University, Seoul, South Korea.

Abstract

Infectious laryngotracheitis virus (ILTV), gallid herpesvirus 1causes mild to severe upper respiratory disease in chickens.Live attenuated vaccines to control ILTV outbreaks have been developed usingserial passages in chicken embryos (CEO) or tissue cultures (TCO) and the CEO vaccines have been using intensively worldwide. However, the CEO vaccinescould acquire virulence through bird-to-bird passages, while the TCO vaccine could not be virulent. The TCO vaccinehas not been registered in Korea. In this study, we developed aTCO vaccine for ILTVwith theKorean virulent field strain. Attenuation of the virulent field strain achievedthrough thirty times of serial passage of the parent stain in LMH cells. After serial passage, three times of pock purifications on chorioallantoic membrane were performed to select pocksthat produced significantly smaller size than those of the parent strain. A safety and efficacy test for two vaccinecandidates were performed in specific-pathogen-free (SPF) birds. Fiftyof six-week old SPF chickens were randomly assigned to five groups. Vaccination was performed via eye-drop method with TCO vaccine candidatesanda commercial CEO vaccine(104 EID50/bird). The all birds were challenged at 2 weeks post vaccination. TCO vaccine candidates were safer than the commercial CEO vaccine. However, vaccine efficacy of the TCO vaccines was less than that of the commercial CEO vaccine. The developed TCO vaccine will allow alternative vaccine program, which can be applied variable conditions of poultry flocks in the Korean field.

Time:

Title: Applying a Radioprotective Mn2+ Peptide Complex (MDP) to the Preparation of Irradiated Vaccines

Elena Gaidamakova
Uniformed Services University of the Health Sciences, USA

Biography

Abstract

Antioxidant Mn2+-peptide complexes accumulated in the extremely radiation-resistant bacterium Deinococcusradiodurans have a remarkable ability to protect and preserve the structure and functions of proteins exposed to megadoses of ionizing radiation, but they do not significantly protect nucleic acids (Daly et al., 2010). Reconstituted D. radiodurans Mn2+-peptide complexes were shown to uncouple protein damage from DNA/RNA damage during supralethal exposures to gamma-radiation and applied to the preparation of irradiated vaccines. An ideal whole-organism vaccine lacks any infectivity, but retains all original epitope configurations needed to mount a protective immune response. We rationally-designed the peptide component of Mn2+-peptide-orthophosphate complexes. One Mn2+-complex named MDP (Mn2+-DEHGTAVMLK-Pi) preserves antigenic structures in aqueous preparations of lethally-irradiated bacteriophage lambda, Venezuelan equine encephalitis virus (VEEV), and methicillin-resistant Staphylococcus aureus (MRSA). MDP-Irradiated vaccines for MRSA protected mice against MRSA skin infection. This novel approach now has been successfully applied to other pathogens.

Time:

Title: A hepatitis B vaccine with a novel adjuvant SBP (HBsAg-binding protein)

Su Caixia
Fudan University, China

Biography

Engineering Doctor student in Biotechnology & Bio-Pharmcy, State key lab of genetic engineering, College of Life Sciences, Fudan University Shanghai 200433, PR China. Ms. Su has worked in R&D of diagnostic reagents, monoclonal antibodies, cytokines, vaccines and other biological products for over twenty years. She is focused on R&D hepatitis B, E and HPV vaccine in recent years. She led the team to have gotten 5 production licenses and 2 clinical approvals related to recombinant hepatitis B vaccine. Now HEV and HPV vaccines are in preclinical research.

Abstract

In general, adjuvants play a very important role in vaccine. SBP is a HBsAg-binding protein which is screened out from human liver cDNA expression library. SBP has been confirmed to promote dendritic cells (DC) to phagocytize HBsAg more effectively and enhance the immunogenicity. These results suggest that SBP could be developed into a safe and promising adjuvant of Hepatitis B vaccine. In this study, the secretory SBP recombinant Pichia pastroris strain is cultured and fermentated, then SBP is purified from fermentation supernatant. The proportion of SBP in hepatitis B vaccine (Hansenula Polymorpha ) is studied, finally a hepatitis B vaccine with the novel adjuvant SBP is manufactured and tested totally according to the requirements. All of the test items are qualified. Its safety, efficacy and stability are evaluated. The efficacy is significantly superior than the control vaccine. The safety and stability are qualified. The results indicate that the novel Hepatitis B vaccine is expected to overcome nonresponsiveness and hyporesponsiveness in a significant number of individuals , and to shorten the hepatitis B vaccine standard 3-dose vaccination regimen to 2-dose regimen, which need to be validated by clinical trials.

Time:

Title: A trivalent recombinant vaccine candidate against brucellosis

Sonal gupta
Jawaharlal Nehru University, India

Biography

Sonal Gupta she is working as a Ph.D research scholar at Jawaharlal Nehru University. She has completed her Masters in biotechnology from the same university. Before that she worked as a research scholar Her research interest is in cloning,Microbiology and Immunology

Abstract

Brucellosis is caused by Gram-negative bacteria of the genus Brucella, which infect different domestic and wild animals. So far, there is no available vaccine which is safe enough for humans. On this point, subunit recombinat vaccine has become the new breakthrough for combating brucellosis. The main goals of the present study include determining the prophylactic potential of a trivalent protein mixture consisting of BP26, Omp25 and L7/L12 ribosomal protein of Brucella abortus as a vaccine candidate against brucellosis. Merit of the Bp26 periplasmic protein is that it is conserved throughout the Brucella genus. It induces a strong Th2 response with mild increase in IFN-gamma levels. Ribosomal protein of Brucella L7/L12 is highly conserved protein in Brucella species and found to be highly immunodominant in the infected cattle. Also, Outer membrane protein 25 (Omp 25) is a highly conserved protein in Brucella sp. which is studied to be involved in virulence of Brucella. Therefore, the current work deals with the co immunization of mentioned 3 proteins following two different quantitative dose statistics for immunization in the mice; “40µg rL7/L12+40µg rBp26+30µg rOmp25 (Mixture 1)” and “20µg rL7/L12+20 µg rBp26+15 µg rOmp25 (Mixture 2)”. Here we show humoral immune response elicited by different mixtures, Mixture 2 (40 µg rL7/L12 + 40 µg rBp26 + 30 µg rOmp25) is similar to Mixture 1 (20 µg rL7/L12 +20 µg rBp26 + 15 µg rOmp25) in multivalent vaccine combination. It was observed that total IgG antibody response in tripartite vaccine was comparable to the mice immunized with Bp26, Omp25 and L7/L12 individually. Good Humoral and cellular immune response was elicited, suggested by higher IgG1 and IgG2 levels in mice immunized with trivalent protein combination.Thus, the simultaneous immunization with three antigens did not appear to diminish immune responses against its components.We also compare the cellular mediated immune response in trivalent vaccine immunized mice to individual protein immunized mice. Also, subunit vaccine is particularly safe for administration in humans and therefore can be used as a vaccine against human brucellosis. Therefore, this study suggests future application of this trivalent protein as an improved vaccine candidate against Brucella species infection.

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Title: Immune response and antibody persistence in goats following vaccination with contagious caprine pleuro-pneumonia F38 Biotype vaccine

Alexander Kipronoh
Agricultural and Livestock Research Organization Perkerra Research Center, Kenya

Biography

Abstract

A post vaccination assessment of contagious caprine pleuro-pneumonia serum antibody persistence following vaccination withCaprivax® F38 Biotype vaccine was conducted at the Kenya Agricultural and Livestock Research Organization - Perkerra Research Center between the months of April, 2014 and March, 2015 to determine the effectiveness of the vaccination program in place. A total of 42 goats of different ages were recruited and put in a longitudinal study with two groups; the vaccine group and non-vaccine group considered as negative control. A baseline assessment of antibody titre was done prior to administration of treatments. Post vaccination serum sampling was conducted monthly and antibody titres assessed using monoclonal antibody based competitive Enzyme-linked immuno-sorbent assay. A significantly higher mean percentage inhibition titre of 71.8% was recorded in goats in the vaccine group compared to 58.6% in goats in the non-vaccine group (p ˂ 0.0001). The magnitude of the difference in the mean percentage inhibition titre levels was large (eta squared = 0.847) indicating a large effect of vaccination in antibody titre levels and hence the effectiveness of using the Caprivax® vaccine. Mortalities were recorded in goats in young age category that received the vaccine for the first time in life, suggesting the need for a repeat vaccination to improve protection using this vaccine

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Title: Protective efficacy of a prime-boost protocol using H5-DNA plasmid as prime and inactivated H5N2 vaccine as the booster against the Egyptian avian influenza challenge virus

Basem Ahmed
Cairo University, Egypt

Biography

Basem Ahmed is the assistant lecturer of Virology from Faculty of Veterinary medicine in Cairo university.His main Research interest is in Molecular Virology, Vaccinology, Immunology.

Abstract

In this study, a recombinant DNA plasmid was constructed, encoding for HA1 of a selected Egyptian H5N1 virus (isolated during the 2012 outbreaks). In the immunization and challenge experiments, SPF chickens received 1 or 2 doses of H5-DNA plasmid prime, and boosted with the inactivated H5N2 vaccine. Haemagglutination inhibition (HI) titers, protection levels, and the magnitude of virus shedding were compared to that of the chickens that received either DNA plasmid or inactivated H5N2 vaccine alone. H5N1 virus A/chicken/Egypt/128s/2012 (H5N1) HPAI clade 2.2.1/C was used for the challenge. Chickens immunized with 1 or 2 doses of H5-DNA vaccine failed to overcome the challenge with 0% and 10% protection, respectively. Quantitative real-time reverse transcription-PCR revealed virus shedding of 2.2 x 104 PCR copies/ml 3 days post challenge (dpc) in the only surviving bird from the group that received 2 doses of plasmid. However, chickens immunized with 1 or 2 doses of H5-DNA plasmid as prime and inactivated H5N2 vaccine as booster, showed 80% protection after challenge, with a viral shedding of 1.2 x 104 PCR copies/ml (1 dose) and 1.6 x104 PCR copies/ml (2 doses) 3 dpc. The surviving birds in both groups did not shed the virus at 5 and 7 dpc. In H5N2-vaccinated chickens, protection levels were 70% with relatively high virus shedding (1.8x 104 PCR copies/ml) 3 dpc. HI titers were protective to the surviving chickens. This study reports the efficacy of H5-DNA plasmid to augment reduction in viral shedding and to provide better protection when applied in a prime-boost program with the inactivated AI vaccine. Keywords. avian H5N1 influenza; inactivated H5N2 vaccine; DNA plasmid; hemagglutinin; prime-boost

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Title: Establishing micro-neutralization assays for human viruses using a quantitative PCR endpoint

Keith Peden
Food and Drug Administration, USA

Biography

Establishing micro-neutralization assays for human viruses using a quantitative PCR endpoint

Abstract

Development of vaccines against emerging and re-emerging human pathogenic virusesis a public health imperative. As most licensed vaccines are effective through eliciting neutralizing antibodies, assays that can quantify neutralizing antibodies will likely be crucialin demonstratingvaccineeffectiveness. Neutralization assays traditionallyinvolve infectious virus, and the assay most commonly used is the plaque-reduction neutralization test. For viruses that can be propagated under standard laboratory conditions, such as Biological Safety Level 2 (BSL-2) conditions, the native virus can be used. This is the case for flaviviruses, such as Zika virus (ZIKV). However, for select agents such as Ebola virus (EBOV), this must be doneunder BSL-4 conditions. Because BSL-4 laboratories are uncommon, we have taken an alternative approach. Our approach uses a replication-competent hybrid virus whose genome carries the envelope gene from the pathogenic virus on the genetic backbone of a non-pathogenic virus. We use vesicular stomatitis virus (VSV), since VSV has the advantage that it can, once its own envelope gene is deleted, accommodate envelope genes from various virusesandincorporate this envelope into the viral particle. The resulting chimeric virus uses the heterologous envelope for entry and is neutralized by antibodies that neutralize the native virus. We have constructed hybrid VSVs carrying the envelope genes for several filoviruses. The readout for infectivity is by reverse transcriptase quantitative PCR (RT-qPCR), an approach we established for other viruses. The primers are directed against VSV genome rather than against the specific envelope gene, and thus the assay can be readily adapted to any virus whose envelope can be incorporated into the VSV particle. There are several advantages of our method. First, using PCR as readout allows the assay results to be obtained within 24 hours and frequently within 8 hours. Second, the sample for the assayis a crude lysate from the infected cells, which obviates the need to purify the nucleic acids and thus the assay is amenable to automation and high throughput. Third, the assay as done is in 96-well format, but could be adapted to a 384-well format for the evaluation of multiple sera. To demonstrate the utility of the approach, we have assessed neutralizing antibodies against several filoviruses and have shown that the antibody titersobtained using our assay are in agreement with those obtained using other assays. Thus, we conclude that our approach could be an alternative to other neutralization assays.

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Title: Effect of methylprednisolone injection on interleukin-4 and interferon-gamma expression following hepatitis B vaccination in mice

Peter Ughachukwu
ChukwuemekaOdumegwuOjukwu University, Nigeria

Biography

Dr. Peter O. Ughachukwu is a Senior Lecturer in the Department of Pharmacology and Therapeutics, ChukwuemekaOdumegwuOjukwu University, Nigeria. He holds MB,BS; as well MSc; and PhD (immunopharmacology) degrees. His research interests include immunotherapy, vaccines, and phytotherapy. He was the immediate past Dean, Faculty of Basic Medical Sciences, and presently, Head, Department of Pharmacology and Therapeutics, ChukwuemekaOdumegwuOjukwu University. Principal researcher, TETFund sponsored research titled ‘Effect of aqueous leaf extract of Ocimumgratissimum on antiretroviral drug-induced hepatotoxicity in rats’. He has twenty four journal articles, most of which as principal researcher. He was Medical Officer of Health, Idemili North Local Government, Anambra State, Nigeria; Fellow, Institute of Public Administrators (FCAI), and pioneer chairman, Life Watch Africa.

Abstract

Background: The prevalence of hepatitis B infection is high worldwide with liver cirrhosis and hepatocellular carcinoma as important complications. Immunosuppression, especially from corticosteroids, is often cited as a cause of poor immune response and there are documented evidences of irrational administration of glucocorticoids to children and adults. Decreased expression of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) is an indication of poor humoral and cellular immune responses respectively. Therefore, we decided to find out if methylprednisolone injection decreases interleukin-4 and interferon-gamma expression following hepatitis B vaccination in mice. Methods: Mice were randomly divided into 2 groups. Daily intramuscular injections of methylprednisolone (15mg/kg) were given to the test group while water for injection (0.1ml) was given to control group for 30 days. On day 6 all mice were given 2 μg(0.1 ml) hepatitis B vaccine and a booster dose on day 27. On the 34th day all mice were anaesthetized, one at a time, using intramuscular ketamine and diazepam 50 mg/kg and 5 mg/kg respectively, and blood samples collected and analyzed for IL-4 andIFN-γ titres using enzyme linked immunosorbent assay (ELISA).The mean values (± S.E.M.) for the generated data was calculated. D’Augostino and Pearson omnibus normality test was performed on the data. Test of statistical significance between test and control groups of mice was done for IFN-γ and IL-4 using Mann-Whitney test. All statistical tests were done using Graph Pad Prism 5.0 and the results taken as statistically significant if the p value < 0.05. Results: The mean ±S.E.M serum IL-4 (pg/ml) for male test, male control, female test, female control were 9.30 ± 4.56, 5.21 ± 1.94, 29.21 ± 10.22, and 14.96 ± 8.97 respectively. The mean ± S.E.M serum IFN-γ (pg/ml) for male test, male control, female test, female control were 8.18 ± 3.47, 7.19 ±2.42, 13.98 ± 3.92, and 13.27 ± 6.70 respectively. These differences in IL-4 and IFN-γtitres in thegroups were not statistically significant. Conclusion: At the dosages and length of exposure used in this study, methylprednisolone injection did not significantly inhibit IL-4 and IFN-γ expression following immunization against hepatitis B virus in mice. Key words: Hepatitis B vaccine, interleukin-4, interferon-gamma, immune response, methylprednisolone.

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