Day 1 :
Time : 09:10-09:50
Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development. Geert then moved on to join the Bill & Melinda Gates Foundation’s GH Discovery team as SPO and later on to work with GAVI as Senior Ebola Program Manager; he subsequently joined the German Center for Infection Research as Head of the Vaccine Development Office. Geert is now primarily serving as a Biotech/ Vaccine consultant while also conducting his own research on NK cell-based vaccines. His work is driven by a relentless passion to translate scientific breakthrough findings into competitive vaccine products. As a creative thinker, innovator, entrepreneur and visionary, Geert has been invited to speak at multiple international congresses.
Immunologists have learned a tremendous amount from vaccinologists but learnings in the opposite direction have been rather poor. Despite the development of a multitude of new vaccine technologies, current vaccine approaches are still empirical and very much focused on inducing measurable immune responses that mimic those induced upon natural infection and which correlate with natural protection. Hence, modern contemporary vaccines are primarily using recombinant or synthetic antigens that bind to the MHC peptide-binding groove (so-called ‘conventional’ antigens) to induce ‘foreign-centered’ immune responses (i.e., antibodies and T cells). ‘Modern’ vaccinology rarely takes into consideration the ground-breaking knowledge and insights gained since many years by immunologists and molecular epidemiologists on how pathogens have evolved immune subversive mechanisms to adapt to their natural host such as to ensure their replication and propagation. As a result of this dogma-driven ignorance, the vaccine field continues to struggle with very little progress made in the fight against infections and immune-mediated or immune-tolerated diseases other than the notorious ‘low-hanging fruit’. It is, therefore, high time for vaccine makers to shift gears and translate some critical epidemiological and immunological knowledge on host-pathogen interactions and the immune pathogenesis of infectious or immune-mediated diseases into truly rational vaccine approaches. There is an increasing consensus that in order for vaccinologists to succeed in driving a safe immune defense strategy that is no longer frustrated by natural infection or naturally occurring immune-mediated disease, vaccines should elicit immune responses that are fundamentally different from those induced upon natural infection or other immune subversive diseases. Hence, it will be paramount for vaccinologists to become better informed and more knowledgeable about the molecular mechanisms underlying immune evasion mechanisms of pathogens in order to design vaccines that are more likely to prevent pathogenic agents from escaping vaccine-mediated immune responses.
N4 Pharma Plc., United Kingdom
Time : 09:50-10:30
As a trained immunologist and virologist, Melody Sauerborn entered the fascinating world of biologics during her PhD. She focused on investigating why biologics induce the formation of anti-drug antibodies. After obtaining her PhD, Dr. Sauerborn established herself in the areas of bioanalysis and immunogenicity by spending numerous years in CROs and biotech companies. She worked predominantly on developing and validating ligand-binding and cell-based assays for PK/Tox and immunogenicity studies for biologics, biosimilars and vaccines. During her role as the head of non-clinical development at Mymetics, a viral vaccine company, she also extended and added to her expertise the production of biologics, vaccines and ATMPs and the aspects of potency assays and GMP. Currently Dr. Sauerborn focuses as a freelance on projects including (non-) clinical immunogenicity assessment, PK/PD assays, production of vaccines and biologics and teaching bioanalytical method validation workshops across Europe (and sometimes beyond).
Currently, there are a number of vaccine types on the market, including live-attenuated, killed, recombinant and subunit vaccines. Each of these vaccine types come with disadvantages such as safety, need of an adjuvant and the need of a cold chain. In order to overcome these shortcomings, nucleic acid vaccines, mRNA and DNA based, are gaining in popularity and starting to populate the pre-clinical and clinical pipelines.
Advantages of these types of vaccines are the potential to trigger both the cellular and humoral immune response and a more efficient manufacturing process. Despite the progress that have been made in the last years with regards to nucleic acid vaccines, in vivo stability remains an issue and a delivery system may be needed.
This keynote lecture will start off with a status quo of nucleic acids and then expand into the delivery systems, and in specific, non-viral delivery systems such as lipid nanocarriers.
The pros and cons of these vaccines and delivery systems will be presented and discussed, ending with a preview of the future of vaccines.
MRGN Advisors, Switzerland
Keynote: Driving behaviors of the stakeholders involved in vaccine value chain through technological advances
Time : 10:30-11:10
Pierre A. MORGON is the Founder of MRGN Advisors. He is Chairman of the boards of Theradiag and of Virometix and he is Non-Executive Director at the boards of Eurocine Vaccines, Vaccitech and Univercells. He is also Regional Partner for Switzerland at Mérieux Equity Partners. He holds a Doctorate of Pharmacy, a Master in Business Law and a MBA. He is also an alumnus of INSEAD, IMD and MCE executive programs.
The vaccine segment is anticipated to be one of the fastest growing one of the healthcare industry and several leading firms have stepped up vaccine investments in recent years. Unlike therapeutic agents, vaccines are administered to healthy individuals only once or very infrequently during a life time. Vaccines generate well-documented positive externalities, yet their poor awareness and acceptability among vaccine end-users may contribute to resurgence of transmissible diseases and consequently trigger governmental interventions such as mandating vaccination.
In addition to technical and clinical development per the highest quality standards, bringing new vaccines to market requires carefully orchestrated programs targeting the multiple types of stakeholders along the entire value chain and addressing their respective purchasing behavioral drivers.
Against a backdrop of anti-vaccination buzz and vaccine fatigue, successful global launch and sustainable usage of a vaccine requires the development of a multi-pronged strategy addressing all aspects in relation to acceptability (e.g. the motivation to immunize despite the quasi-disappearance of the disease), accessibility (e.g. supply chain services), availability (e.g. mechanisms ensuring reliability of supply) and affordability (e.g. tiered pricing policy taking country differences in per capita income into account). Leveraging novel technological advances can positively influence the ability to activate these levers successfully.
Networking & Refreshments 11:10-11:25 @ Foyer
Eclaire MD Foundation, USA
Time : 11:25-12:05
The author received an honorable PhD in mathematics and majored in engineering at MIT. He attended different universities over 17 years and studied seven academic disciplines. He has spent 20,000 hours in T2D research. First, he studied six metabolic diseases and food nutrition during 2010-2013, then conducted research during 2014-2018. His approach is “math-physics and quantitative medicine” based on mathematics, physics, engineering modeling, signal processing, computer science, big data analytics, statistics, machine learning, and AI. His main focus is on preventive medicine using prediction tools. He believes that the better the prediction, the more control you have.
Math-physical medicine approach (MPM) utilizes mathematics, physics, engineering models, and computer science in medical research. Initially, the author spent four years of self-studying six chronic diseases and food nutrition to gain in-depth medical domain knowledge. During 2014, he defined metabolism as a nonlinear, dynamic, and organic mathematical system having 10 categories with ~500 elements. He then applied topology concept with partial differential equation and nonlinear algebra to construct a metabolism equation. He further defined and calculated two variables, metabolism index and general health status unit. During the past 8.5 years, he has collected and processed 1.5 million data. Since 2015, he developed prediction models, i.e. equations, for both postprandial plasma glucose (PPG) and fasting plasma glucose (FPG). He identified 19 influential factors for PPG and five factors for FPG. He developed the PPG model using optical physics and signal processing. Furthermore, by using both wave and energy theories, he extended his research into the risk probability of heart attack or stroke. In this risk assessment, he applied structural mechanics concepts, including elasticity, dynamic plastic, and fracture mechanics, to simulate artery rupture and applied fluid dynamics concepts to simulate artery blockage. He further decomposed 12,000 glucose waveforms with 21,000 data and then re-integrated them into three distinctive PPG waveform types which revealed different personality traits and psychological behaviors of type 2 diabetes patients. Furthermore, he also applied Fourier Transform to conduct frequency domain analyses to discover some hidden characteristics of glucose waves. He then developed an AI Glucometer tool for patients to predict their weight, FPG, PPG, and A1C. It uses various computer science tools, including big data analytics, machine learning, and artificial intelligence to achieve very high accuracy (95% to 99%).
- Hsu, Gerald C. (2018). Using Math-Physical Medicine to Control T2D via Metabolism Monitoring and Glucose Predictions. Journal of Endocrinology and Diabetes, 1(1), 1-6.
- Hsu, Gerald C. (2018). Using Math-Physical Medicine and Artificial Intelligence Technology to Manage Lifestyle and Control Metabolic Conditions of T2D. International Journal of Diabetes & Its Complications, 2(3),1-7.
- Hsu, Gerald C. (2018). Using Signal Processing Techniques to Predict PPG for T2D. International Journal of Diabetes & Metabolic Disorders, 3(2),1-3.
- Hsu, Gerald C. (2018). Using Math-Physical Medicine to Study the Risk Probability of having a Heart Attack or Stroke Based on 3 Approaches, Medical Conditions, Lifestyle Management Details, and Metabolic Index. EC Cardiology, 5(12), 1-9.
Stanford University, USA
Keynote: Structural studies on Carbapenem-Hydrolyzing Class D serine β-Lactamases from Acinetobacter baumannii
Time : 12:05-12:45
Clyde Smith has over 30 years’ experience in the determination of small molecule and protein structures using X-ray crystallography. Dr Smith gained his PhD in Protein Crystallography at Massey University (New Zealand) in 1993, where he studied the structure and metal binding properties of lactoferrin from human milk. He then undertook a two-year NIH-funded postdoctoral fellowship at the University of Wisconsin, working on the structure of the major skeletal muscle protein, myosin. He returned to New Zealand as a FRST postdoctoral fellow studying the structures of thermostable enzymes. In 1997 he was appointed as a Lecturer in Biochemistry in the School of Biological Sciences at the University of Auckland. In late 2003, he moved to the US to take up a Staff Scientist position in the Chemistry Department at Stanford University, working at the Stanford Synchrotron Radiation Lightsource (SSRL). He is currently a Senior Staff Scientist at SSRL. His scientific research in the field of structural biology includes work in antibiotic resistance, folate metabolism and vitamin B12 chemistry.
The class D serine β-lactamases comprise a superfamily of almost 800 enzymes capable of conferring high-level resistance to β-lactam antibiotics, predominantly the penicillins including oxacillin and cloxacillin. In recent years it has been discovered that some members of the class D superfamily have evolved the ability to deactivate carbapenems, “last resort” β-lactam antibiotics generally held in reserve for highly drug resistant bacterial infections. These enzymes are collectively known as Carbapenem-Hydrolyzing Class D serine β-Lactamases or CHDLs (1). The mechanism of β-lactam deactivation by the class D serine β-lactamases involves the covalent binding of the antibiotic to an active site serine to form an acyl-enzyme intermediate (acylation). This is followed by hydrolysis of the covalent bond (deacylation), catalyzed by a water molecule activated by a carboxylated lysine residue (2). It was initially thought that the carbapenems acted as potent inhibitors of the class D enzymes since the formation of the covalent acyl-enzyme intermediate effectively expelled all water molecules from the active site, thus preventing the deacylation step. Our structural studies on two CHDLs (3,4) have indicated that their carbapenem hydrolyzing ability may be due to two surface hydrophobic residues which allow for the transient opening and closing of a channel through which water molecules from the milieu can enter the binding site to facilitate the deacylation reaction (Figure). Although the hydrophobic residues responsible for the channel formation are present in all class D β-lactamases, sequence and structural differences nearby may be responsible for the evolution of carbapenemase activity in the CHDLs. These mechanisms will be presented, including some insights into the carbapenemase activity of non-Acinetobacter CHDLs which show a variation in how deacylation is activated. Future work aimed at improved inhibitor design will also be explored.
1. Queenan, A.M., & Bush, K. (2007) Carbapenemases: The versatile β-lactamases. Clin. Microbiol. Rev. 20, 440- 458.
2. Golemi, D., Maveyraud, L., Vakulenko, S., Samama, J. P., & Mobashery, S. (2001) Critical involvement of a carbamylated lysine in catalytic function of class D β-lactamases. Proc. Natl. Acad. Sci. 98, 14280-14285.
3. Smith, C.A., Antunes, N.T., Stewart, N.K., Toth, M., Kumarasiri, M., Chang, M., Mobashery, S., & Vakulenko, S.B. (2013) Structural basis for carbapenemase activity of the OXA-23 β-lactamase from Acinetobacter baumannii. Chem. Biol. 20, 1107-1115.
4. Toth, M., Smith, C.A., Antunes, N.T., Stewart, N.K., Maltz, L., & Vakulenko, S.B. (2017) The role of conserved surface hydrophobic residues in the carbapenemase activity of the class D β-lactamases. (2017) Acta Crystallogr. D73, 692-701.
Stanford University School of Medicine, USA
Time : 13:35-14:15
A.C. Matin got his PhD from University of California in Microbiology (1969). He is serving as the Chair of MS senate task force on postdoctoral affairs (2009- present), Member of MS senate steering committee (2008-present) & Senator of Medical School senate (2006-present). He is a Fellow of the American Academy of Microbiology. He got 16 Honors and Awards which are Star Award in Environmental Protection Agency (1991-1997), Review Committee Member in Accreditation Board for Engineering and Technology (1992) and Foundation for Microbiology Lecturer in American Society for Microbiology (1991-1993). He has authored about 37 Publications that include review articles. His Community & International Work involved in Bacterial antibiotic resistance in space flight, Stanford University; NASA Ames and Nuclear waste remediation.
Statement of the problem: Bacterial antibiotic resistance is a world-wide public health problem requiring and new approaches. Background: Sigma S (σs) controls the synthesis of proteins that contribute to the resistance of bacteria like uropathogenic Escherichia coli (UPEC) in the stationary phase of growth, where bacteria are most virulent; σs is encoded by the rpoS gene. Methodology: Colony forming unit formation was used to determine antibiotic sensitivity; a novel microfluidic device determined sensitivity at single-cell level. Results: Lack of rpoS increased UPEC sensitivity to bactericidal antibiotics: gentamicin (Gm), ampicillin and norfloxacin. Gm will be discussed to illustrate the findings with the three antibiotics. Global proteomic analysis implicated weakened antioxidant defense. Use of the psfiA genetic reporter, 3-(p-hydroxyphenyl) fluorescein (HPF) dye, and Amplex Red showed that Gm generated more oxidative stress in the mutant. Cell elongation can compromise the results of HPF, but the antibiotic treatment did not affect the dimensions of stationary phase bacteria. The antioxidant, N-acetyl cysteine (NAC), & anaerobiosis decreased drug lethality. Thus, greater oxidative stress caused by insufficient quenching of endogenous ROS and/or respiration-linked electron leakage contributed to the increased sensitivity of the mutant; this was confirmed also in vivo. Eliminating of quencher proteins, SodA/SodB and KatE/SodA, or the pentose phosphate pathway proteins, Zwf/Gnd and TalA, (source of NADPH required by the quenchers), also generated greater oxidative stress and killing by Gm. The results were confirmed at single-cell level, as well as under microgravity during space flight where astronaut immune response is compromised. Conclusion and Significance: Besides their established mode of action, bactericidal antibiotics also kill bacteria by oxidative stress. Targeting the antioxidant defense will therefore enhance their efficacy. Bioinformatic approaches have identified small molecules that inhibit these proteins and are under study.
- J-H Wang, R Singh, M Benoit, M Keyhan, M Sylvester, M Hsieh, A Tathireddy, Y-J Hsieh, AC Matin. 2014. Sigma S-dependent antioxidant defense protects stationary phase Escherichia coli against the bactericidal antibiotic gentamicin. Antimicrob. Agents Chemother. 58(10): 5964-5975
AC Matin, J-H Wang, Mimi Keyhan, Rachna Singh, Michael Benoit, Macarena P. Parra, Michael R. Padgen, Antonio J. Ricco,* Matthew Chin, Charlie R. Friedericks, Tori N. Chinn, Aaron Cohen, Michael B. Henschke, Timothy V. Snyder, Matthew P. Lera, Shannon S. Ross, Christina M. Mayberry, Sungshin Choi, Diana T. Wu, Ming X. Tan, Travis D. Boone, Christopher C. Beasley, and Stevan M. Spremo. Payload hardware and experimental protocol for testing the effect of space microgravity on the resistance to gentamicin of stationary-phase uropathogenic Escherichia coli and its ss-deficient mutant. Life Sciences in Space Research 15: 1-10 (2017).
- Fengjiao Lyu; Ming Pan; Sunita Patil; Jing-Hung Wang; A. C Matin; Jason R Andrews; Sindy K.Y. Tang. 2018. Phenotyping antibiotic resistance with single-cell resolution for the detection of heteroresistance. Sensors & Actuators: B. Chemical 270 (2018) 396–40.