Day 1 :
University of California, USA
Time : 09:30-10:00
Michael G. Agadjanyan is currently the Vice President, Professor and Head of the Department of Molecular Immunology at the Institute for Molecular Medicine, HuntingtonrnBeach, California and Adjunct Professor at the MiND Institute at UCI. He was formally a Visiting Professor at the Wistar Institute and at the University of Pennsylvania,rnPhiladelphia, PA. Before coming to the US in 1991 he was a Professor at the Mechnikov’s Institute for Vaccines and Sera in Moscow at the Russian Academy of Medicine.rnIn the last 25 years he has received numerous grants from the NIH as well as foundations such as the Susan G. Komen Foundation, and the Alzheimer’s Associationrnsupporting studies for the generation of humanized monoclonal antibodies and vaccines.
Traditional vaccination against infectious diseases relies on generation of cellular and humoral immune responses that actrnto protect the host from overt disease even although they do not induce sterilizing immunity. More recently, attempts havernbeen made with mixed success to generate therapeutic vaccines against a wide range of non-infectious diseases including allergy,rncancer, diabetes, drug addiction and autoimmune diseases, amongst others. However, amongst the most radical innovations wasrntherapeutic vaccination for neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease. Followingrnthe exciting first report in 1999 of successful vaccine prevention of progression of an AD animal model, various vaccines targetingrnbeta amyloid (Aβ) have progressed to human clinical trials, with mixed results. More recently, AD vaccines based on tau proteinrnhave advanced into clinical testing.rnWhile a successful AD vaccine remains tantalizing close the mixed results obtained so far in clinical trials of AD vaccinesrnincluding many difficulties and misconceptions encountered on the path to a successful AD vaccine will be presented. Morernspecifically, we will discuss requirement of (i) better standardization of immunological efficacy measures of anti-Aβ and anti-taurnvaccines, (ii) better methods to improve vaccine immunogenicity such as novel adjuvants and the design of AD vaccines, (iii) thernmost promising strategies for using active immunization targeting Aβ and/or tau pathological proteins for prophylaxis and/orrnprevention of early AD progression.
Co-founder Principal and Chief Scientific Officer Mucosal Immunologist and Vaccinologist EpitoGenesis, Inc. USA
Keynote: Immunomodulatory Properties of Vitamins and Flavonoids as Vaccine adjuvants Against Infectious Diseases
Time : 10:00-10:30
Dr. Michael Vajdy is Co-founder, President and Chief Scientific Officer of EpitoGenesis, Inc., established in 2008. Dr. Vajdy is a Mucosal Immunologist and Vaccinologist with over 24 years of academic and industry experience in designing mucosal and systemic adjuvants and vaccines, studying mechanisms of mucosal and systemic immune induction, long-term immunological memory, and product development. Following his Ph.D. Studentship at Goteborg University under the supervision of Dr. Nils Lycke, a prominent mucosal immunologist, Dr. Vajdy completed postdoctoral fellowships at Loyola University Chicago with Dr. Katherine Knight, then President of the American Association of Immunology and at Harvard Medical School with Dr. Marian Neutra, a renowned expert in mucosal biology and M cells of the intestinal Peyer’s patches and mucosal HIV vaccine development. Dr. Vajdy was recruited to Chiron Corporation (later Novartis Vaccines and Diagnostics, Inc.) where his work was instrumental in the development of mucosal and systemic vaccine products against various infectious diseases. He remained there for 9.5 years with increasing responsibilities including project leadership for a vaccine manufacturing platform technology. He also held simultaneous academic positions as Adjunct Clinical Assistant Professor with the Department of Internal Medicine, Division of Infectious Diseases and Visiting Associate Professor at Department of Medical Microbiology and Immunology, University of California, Davis. He was also a Faculty member with the graduate group, Department of Comparative Pathology, University of California, Davis. In these capacities, he trained student/fellows and wrote collaborative NIH grants. Dr. Vajdy has authored over 55 peer reviewed manuscripts and book chapters; he is the editor of a book entitled “Immunity against Mucosal Pathogens” (Springer, 2008) and has been PI or Investigator on several NIH grants. He is currently an Adjunct Full professor at the Department of Pathobiology, University of Connecticut.
During the past decades, Immunologists and Vaccinologists have used in vitro and in vivo models to identify and characterize immunomodulating activities of potential vaccine adjuvants and delivery systems. Intense research in vaccine adjuvant discovery has focused on toll like receptors, mutant toxins and viral and bacterial vectors. However, recent evidence suggests that nutritive components such as vitamins and a subclass of polyphenols also possess immunomodulating properties without the potential toxic side effects of mimicking danger signals in traditional adjuvant research. We have designed a chemically well-defined and GMP-manufacturable Nutritive Immune-enhancing Delivery System (NIDS), as a nano-emulsion, composed of a combination of two vitamins, and a plant based polyphenol in various delivery systems including organic and inorganic pharmaceutically acceptable carriers. We present in vitro and in vivo data to demonstrate paradoxical immunomodulating activities of select vitamins and polyphenols compared to well-known adjuvants. We further demonstrate significant enhancement of adaptive local and systemic immune responses, in the absence of typical proinflammatory cytokines and chemokines, following mucosal and systemic vaccinations with NIDS and compared to the responses following vaccinations with other licensed or in development vaccine adjuvants and delivery systems. Furthermore, we demonstrate that our adjuvant’s mechanism of action is through the action of a single cytokine and its receptor. Our results demonstrate a safer approach to vaccine adjuvant design with the potential to open a new era in the design and development of safe and effective future vaccines.
ARC Australia Professorial Fellow Chair in Biological Chemistry Editor-in-Chief, Current Drug Delivery Editor-in-Chief, Drug Delivery Letters University of Queensland Australia
Keynote: Dendritic Vaccine Delivery Systems
Time : 10:30-11:00
Prof Istvan Toth PhD, DSc ARC Australia Professorial Fellow is a chemical engineer and an internationally recognized expert in drug delivery. His major research interests are immunoadjuvants, carbohydrates, lipids, peptides, nucleosides and nucleotides. At the School of Pharmacy, University of London and at the University of Queensland prof Toth built up a strong, very productive research group where the research orientation well suited the direction of modern multidisciplinary pharmaceutical sciences. All his former PhD students have excellent reputable jobs both at Academia and at Pharmaceutical Industry. He has refereeing duties for many international scientific journals and for scientific granting bodies. He has also demonstrated track record in research commercialization he is a one of key founders of Alchemia (ASX listed), Implicit Bioscience Pty Ltd, Neurotide Pty Ltd and TetraQ. Prof Toth is also a Scientific Advisory Board Member of Implicit Bioscience Pty Ltd. Brisbane, Australia and Proxima Concept Ltd, London, UK. He has obtained a Business/Higher Education Round Table (BHERT) Award: Outstanding Achievement in International Collaborative R&D. Toth has more than 300 peer-reviewed publications and 43 patents. He is the Editor in Chief of Current Drug Delivery; Drug Delivery Letters, Associate Editor of Medicinal Chemistry; Board Member of Mini Reviews in Medicinal Chemistry, Open Drug Delivery, Open Medicinal Chemistry and Current Patents in Drug Delivery; Prof Toth has been appointed as a member of the ARC College of Experts (2008-2010) and has been the funding President of the Australian Chapter of Controlled Release Society. He is a Fellow of the Royal Australian Chemical Institute (FRACI) and the Queensland Academy of Science and Art (FQA).
Subunit vaccines that contain the minimal microbial components necessary to stimulate appropriate immune responses have the potential to overcome allergic response or autoimmunity that can result from using classical vaccines. We developed new delivery systems by combining the adjuvant and antigenic peptide epitopes into one chemically bonded dendritic entity. The presentation of epitopes on the nanoparticles surface was optimized to elicit a strong immune response in mouse models. rn Infection with group A streptococci (GAS), one of the most common and widespread human pathogens, can result in a broad range of diseases, with the potential to develop acute and post-infectious rheumatic fever and rheumatic heart disease. Immunity to GAS relies on the production of opsonic antibodies specific to the hypervariable N-terminal and conserved C-terminal regions of the coiled-coil α-helical M protein, a GAS major virulence factor. To improve vaccine delivery we developed a self-adjuvanting lipid core peptide (LCP) dendrimer system that included the antigen, a T helper epitope, a carrier, and the adjuvant within the same molecular entity. The system allowed the attachment of multiple copies of antigens. We investigated the structural requirements to elicit production of different antibodies (IgA, IgG) and assessed the influence of complex size on the level of antibody production1.rn Recent developments in nanomedicine/vaccinology have identified that size and morphological characteristics of nanoparticle vaccines affect their efficacy. Preliminary investigations have demonstrated that polymer-based nanoparticles that displayed peptide epitopes on their surface induced very strong immune responses against those epitopes. We have also shown that this response was dependent on the size of the total construct. We explored the efficacy of nanoparticle vaccines using a human papillomavirus (HPV) model. HPV infection, most commonly HPV-16, is responsible for the vast majority of cases of cervical cancer, which is the second most common cancer in women worldwide. The development of therapeutic vaccines that eliminate HPV infected cells and eradicate established HPV-associated tumors would therefore be beneficial and desirable. We established a synthetic pathway to conjugate human papillomavirus peptide antigens to the polymeric core to create macromolecular vaccine candidates to treat HPV-related cancers. These conjugates reduced tumor growth and eradicated established E7-expressing TC-1 tumors in mice after a single immunization, without the addition of an external adjuvant2.rn We extended our vaccine delivery platform investigations by using lutenizing hormone-releasing hormone (LHRH) as antigen. An anti-LHRH vaccine aims to control the level of sex hormones FSH and LH by generating antibodies against LHRH in murine and ovine models.rnWe have observed significant IgG antibody response after primary immunization without the use of additional adjuvant. The antibody response was enhanced and longer lasting when we co-administered commercial adjuvant AdjuVacTM [Lab Anim (NY) 2007, 36 (9) 51-58] with our LCP-LHRH vaccine formulation3.rn1) Zaman M, Chandrudu S, Giddam AK, Reiman J, Skwarczynski M, McPhun V, Moyle PM, Batzloff MR, Good MF, Toth I. Group A Streptococcal vaccine candidate: contribution of epitope to size, antigen presenting cell interaction and immunogenicity. Nanomedicine (London). 2014;9(17):2613-26242) rn2) Liu TY, Hussein WM, Giddam AK, Jia Z, Reiman FM, Zaman M, McMillan NAJ, Good MF, Monteiro MJ, Toth I, Skwarczynski M. Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine. Journal of Medicinal Chemistry. 2015;58:888-8963) rn3) Goodwin D, Varamini P, Simerska P, D’Occhio MJ, Toth I. Design, synthesis and evaluation of a gonadotroping releasing hormone-based subunit vaccine in rams (Ovis aries). Vaccine. 2015 Available online 09 Feb 2015rn