USDA, USA
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 hyper immune 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.
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.
USDA, USA
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.
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 micro biome studies in metagenomics and transcriptomics tools.
1Department of Health Services, Nakuru County, Kenya
2Nakuru County Referral Hospital, Kenya
3Njoro Sub County Health Office, Kenya
4Department of Health Services, Kenya
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 (X2 1716.7, p 0.000), non vaccination with influenza vaccine X2 1702, p 0.000) and malnutrition (X2 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.
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.
1CEL-SCI Corporation, USA
2Roseman University of Health Sciences, USA
3,4Rush University Medical Center, USA
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.
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.
1The Biomedical Center, Russia
2Research Institute of Highly Pure Biopreparations, Russia
3iPharma LLC, Russia
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.
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.
Div. Surgical Oncology, North Shore Univ. Hosp / Northwell Health System and Precision Biologics
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 todayʼs 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.
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 1990ʼs, Dr. Arlen helped to found another biotechnology company, International Bio-Immune Systems, Inc. of which he was part of management until 2003.
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, USA
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) and Zika 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.
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).
Lanzhou Veterinary Research Institute of Chinese Academy of Agriculture Science,
State Key Laboratory of Veterinary Etiological Biology,
National Foot-and-Mouth Disease Reference Laboratory, China.
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, itʼs 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 canʼt be used as the seed of vaccine production. Results of sequence analysis indicated that mutants of SL structure in 3ʼUTR 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.
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.
Wuhan University School of Medicine, China
Background: Approximately 2.35% of the worldʼs population is chronically infected with hepatitis C virus (HCV) and eventually 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 glycoprotein 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 protective 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.
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 Zhangʼs 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.
Chinese Academy of Sciences, China
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.
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.
Bionor Pharma ASA, Norway
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.
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 companyʼs lead product, Vacc-4x.
Chief Scientific Officer, Cellular Technology Limited (CTL), USA
Adjunct Associate Professor of Pathology Case Western Reserve University, USA
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 assayʼs 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.
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 CTLʼs GLP- and CLIA compliant contract laboratory for various pharmaceutical and biotechnology clients.
Institute of Human Virology-School of Medicine, University of Maryland, USA
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.
Biography:
Juan Carlos Zapata 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, he identified mutations in the arena virus nucleo capsid protein (NP) that are likely to impact viral pathogenesis and the induction of protective immunity. Additionally, he is involved in a new line of work focusing on retroviral latency. Under Dr. F. Romerio leadership he is working in detecting and characterizing viral factors related with HIV latency in the reservoir cells and with Dr. Y. Tagaya he is implanting patient-derived ATL cells into NSG mice to study cancer pathogenesis, treatment options, and vaccine development against HTLV-1.
Institute for Health Metrics and Evaluation, University of Washington, USA
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.
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).
1Research Centre, CHU Sainte-Justine, Canada
2Department of Microbiology, Infectiology and Immunology, University of Montreal, Canada
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.
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 aspects of Epstein-Barr virus pathogenesis in immunocompromised patients. Dr Alfieriʼs 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.
Food and Drug Administration, USA
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 non immunized control mice. When as few as 105 cells were transferred, a 0.7 log10 CFU reduction was observed 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.
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.
1University of Central Florida, Burnett School of Biomedical Sciences, USA
2University of North Carolina – Chapel Hill School of Medicine, USA
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.
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.
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