Day 1 :
Keynote Forum
Geert Vanden Bossche
VaReCo, Belgium
Keynote: Why don’t our vaccines reach the high-hanging fruit?
Time : 09:10-09:50
Biography:
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.
Abstract:
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.
Keynote Forum
Melody Janssen
N4 Pharma Plc., United Kingdom
Keynote: The future of nucleic acid vaccines and non-viral delivery systems
Time : 09:50-10:30
Biography:
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).
Abstract:
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.
Keynote Forum
Pierre A MORGON
MRGN Advisors, Switzerland
Keynote: Driving behaviors of the stakeholders involved in vaccine value chain through technological advances
Time : 10:30-11:10
Biography:
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.
Abstract:
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
Keynote Forum
Gerald C. Hsu
Eclaire MD Foundation, USA
Keynote: Methodology of math-physical medicine
Time : 11:25-12:05
Biography:
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.
Abstract:
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%).
Recent Publications
- 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.
Keynote Forum
Clyde A Smith
Stanford University, USA
Keynote: Structural studies on Carbapenem-Hydrolyzing Class D serine β-Lactamases from Acinetobacter baumannii
Time : 12:05-12:45
Biography:
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.
Abstract:
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.
Recent Publications
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.
Keynote Forum
A. C. Matin
Stanford University School of Medicine, USA
Keynote: Role of bacterial antioxidant defense in their resistance to bactericidal antibiotics
Time : 13:35-14:15
Biography:
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.
Abstract:
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.
Recent Publications
- 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.
- Human Vaccines - Infectious & Non Infectious Diseases | Vaccine Research & Development | Veterinary Vaccines | Vaccines against Viral & Bacterial Diseases | Vaccines for Respiratory Diseases
Location: Meeting Hall: Wright
Chair
Melody Janssen
N4 Pharma Plc., UK
Session Introduction
Andrea Fritzer
Valneva Austria GmbH, Austria
Title: Chikungunya – A reemerged tropical disease: Development of a live- attenuated vaccine
Time : 14:15-14:45
Biography:
Dr. Andrea Fritzer is currently Senior Scientist at Valneva Austria GmbH, which is a fully integrated, commercial stage biotech company, focused on developing innovative and life-saving vaccines. Andrea has gained in her 13 years working in the field of biotechnology and vaccine research, a broad and solid background in molecular biology, bacteriology, virology and immunology. Additionally, she has worked in the field of therapeutic monoclonal antibody discovery and antibody engineering. Her primary function at Valneva is to coordinate various projects advancing them from preclinical development into clinical studies with focus not only on in vitro assay development but also on the initiation and continuation of research collaborations. Valneva’s chikungunya vaccine VLA1553 is currently her main project where she is supporting the progress of VLA1553 to enter the next clinical phase.
Abstract:
Chikungunya virus (CHIKV) is a mosquito-borne virus resulting in many patients in chronic and incapacitating arthralgia affecting all gender and age groups. CHIKV was typically transmitted by Aedes aegypti mosquitos however, an adaptation enabled unusually efficient transmission by Aedes albopictus mosquitos. Thus, the virus re-emerged in 2004 and rapidly spread over Africa, Asia, the Americas and locally also in Europe since then. CHIKV is regarded as one of the most-likely re-emerged viruses to spread globally. Morbidity due to this virus is considered a serious threat to global public health raising an urgent demand for efficient prophylaxis. However, at present there is no treatment or vaccine available. Facing the unmet medical need for a prophylactic intervention, we initiated a program to develop a vaccine candidate (VLA1553) against CHIKV infections.
Valneva’s live-attenuated CHIKV vaccine candidate, VLA1553, is based on the La Reunion strain of the East Central South African genotype. The Vero cell based vaccine is characterized by a 60 amino acid deletion in the nsP3 viral replicase complex gene leading to attenuation of the virus in vivo.
The safety, immunogenicity as well as protective efficacy of the vaccine candidate was evaluated in mice and non-human primates. We demonstrate, that our vaccine candidate is highly attenuated in animal models and causes no clinical manifestations typically associated with wild-type CHIKV infections in addition to strongly reduced viremia and cytokine levels. Moreover, VLA1553 is highly immunogenic and induces a strong and long-lasting neutralizing antibody response in animal models. In addition, cross-neutralizing antibodies against a Caribbean CHIKV strain are induced. VLA1553 protects against a high dose wild-type CHIKV challenge after a single immunization and no anamnestic response was observed after challenge.
Due to its safe and immunogenic potential we entered into a blinded, randomized phase 1 first-in-human clinical study investigating the safety and immunogenicity of three dose levels administered intramuscularly in a CHIKV-naïve population as a single-shot immunization designed to elicit long-term immunological memory (NCT:NCT03382964).
Recent Publications
-
Hallengärd D, Kakoulidou M, Lulla A, Kümmerer BM, Johansson DX, Mutso M, Lulla V, Fazakerley JK, Roques P, Le Grand R, Merits A, Liljeström P (2014) Novel attenuated Chikungunya vaccine candidates elicit protective immunity in C57BL/6 mice. J Virol 88:2858-2866.
- Roques P, Ljungberg K, Kümmerer BM, Gosse L, Dereuddre-Bosquet N, Tchitchek N, Hallengärd D, Garcia-Arriaza J, Meinke A, Esteban M, Merits A, Le Grand R, Liljeström P (2017) Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus. J Clin Invest Insight 2:e83527.
Anthony Gilbert
hVIVO, UK
Title: The human viral challenge model-accelerating vaccine development
Time : 14:45-15:15
Biography:
Anthony S Gilbert has obtained his Bachelor of Medicine and Bachelor of Surgery degree from the University of the Witwatersrand, South Africa. He is a Member of the Institute of Clinical Research. He has served as an expert Member and Vice Chair of a National Research Ethics Service (NRES) committee, having been appointed by the Health Research Authority in the U.K. As a Principal Investigator, he has supervised and conducted viral challenge studies in order to further the quest to bring safer and more effective vaccines and antivirals to the global community. His research has been published in several medical and scientific journals, including Nature Medicine.
Abstract:
Since the beginning of the millennium, Human Viral Challenge Studies have successfully been conducted at hVIVO to develop a series of well-characterised virus stocks, whilst demonstrating that the Human Viral Challenge Model (HVCM) could be effective in offering a faster and cost-effective route to market for their therapeutics.
The Human Viral Challenge Model enables global pharmaceutical and biotechnology companies, as well as leading academic groups and government institutions, to undertake scientific research, accelerate the drug development timeline and reduce the cost of bringing vaccines, antiviral drugs and diagnostics to market. The HVCM also enables fundamental research into the human response to infection and crucial research into modes of infection and transmission between individuals in the community.
The HVCM has become widely accepted as an alternative to traditional early stage field trials to show the efficacy of vaccine and antiviral therapeutics in Influenza, Respiratory Syncytial Virus (RSV) and Human Rhinovirus (HRV). By monitoring the entire disease lifecycle as subjects move from healthy to sick and recover back to healthy again, we can obtain high quality, longitudinal data from the before, during and after phases of disease. The model can be used to study the efficacy of new therapies and also to study the target disease itself. Such studies provide key outcomes about promising investigational medicinal products, their mechanism of action, and their most appropriate dose and dosage regimen, which can then be applied to design further Phase IIb and Phase III studies.
Recent Publications
1. Wilkinson, Tom M (2012) Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in human. Nature Medicine 18:274–280.
2. DeVincenzo, John P. (2014) Oral GS-5806 Activity in a Respiratory Syncytial Virus Challenge Study. N Engl J Med 371:711-722.
3. DeVincenzo, John P. (2015) Activity of Oral ALS-008176 in a Respiratory Syncytial Virus Challenge Study. N Engl J Med 373:2048-2058.
4. Lambkin-Williams, Rob (2016) An Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine Is Safe, Immunogenic & Efficacious in the Human Viral Influenza Challenge Model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection. Pone 11(12):e016308.
5. Lambkin-Williams, Rob (2018) The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics. Respir Res. 1:123.
Konstantin Chumakov
Food and Drug Administration, USA
Title: Antigenic diversity of type 1 polioviruses and its implications for efficacy of inactivated polio vaccines
Time : 15:15-15:45
Biography:
Konstantin Chumakov works on creation of new methods for development and evaluation of vaccines against viral diseases. His main focus is on studying poliovirus and poliovirus vaccines. It includes application of cutting-edge molecular approaches for monitoring genetic stability and molecular consistency of viral vaccines, as well as on new immunochemical methods for characterization of vaccines and their potency and efficacy. The approaches include next-generation (deep) sequencing for assessing molecular consistency of viral vaccines as well as metagenomic surveillance, development of human monoclonal antibodies and their use for therapeutic and diagnostic purposes.
Abstract:
Statement of the Problem: Two vaccines against poliomyelitis – Inactivated Polio Vaccines (IPV) and live Oral Polio Vaccine (OPV) are among the most successful vaccines ever. They define paradigms for vaccine protection against viral diseases, and brought about virtual elimination of the disease in most of the world. Nevertheless, some questions about the correlates of their efficacy remain. Polio eradication will lead to discontinuation of OPV use and its replacement with IPV. To ensure IPV supply for resource-limited countries a new generation of IPV based on attenuated Sabin strains (sIPV) was developed. This raised important questions about determining its efficacy and potency. How can these new vaccines be compared to the conventional IPV (cIPV) made from immunochemically different strains? Can we use the same benchmarks for potency and protectiveness for both types of IPV? These questions prompted us to undertake the study.
Methodology & Theoretical Orientation: We assembled a panel of wild and vaccine-derived polioviruses and used it to determine titers neutralizing antibodies in sera from healthy previously immunized subjects, as well as in immunized animals. In addition, we have used a transgenic mouse model to determine the minimal level of antibodies needed for protection. Findings: antibodies against poliovirus present in sera of experimental animals as well as healthy vaccinated subjects exhibited a significant strain bias when tested in neutralization reaction. Maximum neutralization titers were observed when neutralization tests were performed against the strain used for vaccine manufacture, while titers against heterologous strains tended to be lower. In some extreme cases the difference in titers was more than 10-fold. As a result, while the level of seroprotection in a group of vaccine recipients was sufficiently high when measured against the homologous strain, it was significantly lower when heterologous strains were used. A booster dose of IPV increased all titers, and the seroprotection level was acceptable even when measured against heterologous strains. We will also present experiments to identify the minimal protective level of neutralizing antibodies by passively immunizing transgenic mice expressing the human poliovirus receptor.
Conclusion & Significance: The results demonstrate that strains of type 1 poliovirus have different ability to be neutralized by vaccine-induced antibodies. This suggests that while people with minimal levels of neutralizing antibodies can be protected against viruses that are immunologically similar to the strains used in vaccine manufacture, they may have undetectable levels of neutralizing antibodies against other strains and thus not be fully protected. Therefore to ensure protection against a wide range of viruses, clinical trials must include measuring seroconversion using both homologous and heterologous strains. The same applies to performing pre-clinical evaluation and measuring potency of IPV, as well as to performing seproprevalence studies. The results also suggest that to ensure robust protection against all strains the level of neutralizing anti-poliovirus antibodies must be maintained at a level higher than the commonly accepted minimum of 1:8.
Lopa Banerjee
Cardiff University, UK
Title: A systematic review investigating the factors that affect the participation of children and adolescents in vaccine research
Time : 16:00-16:30
Biography:
Lopa Banerjee is currently a 22-year-old fourth year medical student at Cardiff University School of Medicine. In 2018, she completed an intercalated BSc in Clinical Epidemiology at Cardiff University, achieving first class honours and being awarded the ‘Deans List Award’. She has been involved with a range of research projects at university including studies on sepsis and Human Immunodeficiency Virus (HIV). She has also been President of Cardiff Students for Global Health, the global health society at Cardiff University and was a Co-Chair for the Organising Committee for the Students for Global Health National Conference on Sexual Health and HIV in 2018, which involved being the lead organiser for a 2 day national student conference.
Abstract:
Introduction: Clinical research requiring participation of children and adolescents, including vaccine research, may be controversial and require greater ethical, legal, and cultural considerations than research involving adults. The aim of this review is to identify the factors (i.e. motivators, barriers, and solutions), which affect the participation (i.e. recruitment and retention) of children and adolescents in vaccine research.
Methods: A systematic review was completed using a search strategy, eligibility criteria, and proforma in a pre-defined protocol submitted to PROSPERO (131360). Papers published up to April 2019, on factors that affect the participation of participants aged 18 years and younger were searched for using seven online databases and hand-searching. Data were extracted using the pre-defined proforma, analysed thematically, and summarised using narrative synthesis.
Results: Of 1216 citations found, 304 full-text articles were reviewed, and 77 papers were included, covering 19 vaccine types from 28 countries. Based on the most frequently occurring reasons, participants and their parents were primarily motivated by their level of understanding, perceived personal benefit, altruism, access to better healthcare, and trust in researchers and healthcare professionals. Barriers included misunderstanding information about the trial, risks of side-effects, mistrust of researchers, conflict between stakeholders (i.e. parents, children and researchers), and fears about trial procedures. Suggested solutions were better education of participants and parents, clear consent and assent processes, and community support.
Conclusion: Many factors that affected participation were identified, with overlap between motivators, barriers and solutions. Literature quantity varied by country and vaccine type, and areas identified for further research were those in which evidence was contradictory or lacking. Utilising age-appropriate consent/assent processes, gaining the support of the entire community, and more effectively delivering information about research and vaccines, both generally, and specifically regarding randomisation, blinding and dispelling therapeutic misconceptions, could improve the participation of children and adolescents in vaccine research.
Keywords – Paediatric Research, Research Participation, Vaccine, Vaccine Research
Mazhar Khan
University of Connecticut, USA
Title: Novel nanoparticle based vaccine against respiratory viruses
Time : 16:30-17:00
Biography:
Prof. Dr. Mazhar I. Khan’s research involved molecular epidemiology and pathogenesis of influenza virus infection. Currently, in his laboratory in developing and testing nanoparticle based avian influenza (bird flu) and infectious bronchitis virus vaccines. He has long-term experience in development and application of DNA probe, PCR, multiplex PCR, real-time PCR and loop-mediated isothermal amplification (LAMP) methods for rapid detection of viral pathogens in clinical samples. Have made significant contributions in the diagnostic field using DNA techniques in identification of several pathogens of avian, animal and human diseases since 1985. Have mentor visiting international scientists form Asia, Europe and South America. He has an extensive knowledge on pathogenicity studies in embryos infected with infectious bronchitis virus, a coronavirus, which causes stunting and embryo deformity before hatching. As a virologist, have extensive knowledge and research involved in the development of diagnostic tests and vaccines for the control of avian viral diseases.
Abstract:
Subunit or DNA vaccines are generally less immunogenic than whole organism vaccines. One approach to reduce this deficiency is the development of repetitive antigen displays. One of the most successful repetitive antigen displays is our Self-Assembling Protein Nanoparticle (SAPN) technology. Based of coiled-coil oligomerization domains our SAPNs can self-assemble into spherical particles that mimic the size and shape of small viruses, decorated on their surface with antigens. We have used SAPNs to develop avian influenza (AI) and infectious bronchitis virus (IBV) vaccines by displaying the two conserved and antigens of these viruses. In case of AI, these M2e and Helix C in their native tetrameric and trimeric oligomerization states, respectively, while B cell epitopes derived from the second heptad repeat (HR2) region of the IBV spike protein are repetitively presented in their native trimeric conformation. In addition, flagellin been co-assembled into the SAPN to achieve a self-adjuvanting effect. Specific Pathogen-Free Chickens vaccinated with such self-adjuvanted SAPNs induce significantly higher levels of antibodies than unadjuvanted SAPNs. Antibodies from chickens vaccinated with the self-adjuvanted SAPNs are cross neutralizing towards group 1 influenza strains in in vitro experiments. Immunization with self-adjuvanted SAPNs provides full protection against lethal human influenza challenge in mice, while, chickens were partially protected against a lethal pathogenic avian influenza. The IBV-SAPN vaccine fully protected chickens against pathogenic IBV. Thus, we have generated self-adjuvanted SAPNs with a great potential as universal human and avian influenza as well as IBV vaccines. Future studies are in progress to improve those SAPN-vaccines and test for cross-protection against various sub or serotypes of influenza and IBV.
Recent Publications
1. Babapoor, S., D. O. Almeida, J. J. Fabis, Z. H. Helal, X. Wang, T. Girshick and M. I. Khan. Protective Effect of In ovo Vaccination with IBV-Spike-Recombinant DNA and Chicken Interferon as an Adjuvant. Int. J. Poult. Sci 8 (11): 1034-1041, 2009.
2. Karch, C., P., J. Li, C. Kulangara, S.M. Paulillo, S.K. Raman, S. Emadi, A. Tan, Z.H. Helal, Q. Fan, M. I. Khan, P. Burkhard, Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge. Nanomedicine: Nanotechnology, Biology and medicine.13: (1), 241-251. 2017.
3. Ebrahimi-Nik H., M. R. Bassmi, M. Mohri, M Rad and M. I. Khan. Bacterial ghost of avian pathogenic E. coil (APEC) serotype o78:K80 as a homologous vaccine against avian colibacillosis. PLOS One, doi.org/10.1371/journal.pone.0194888. March 22, 2018.
4. Li, Jianping. Z. Helal, B. Ladman,C. Karch, J. Gelb, Jr, P. Burkhard and M. I. Khan..Nanoparticle vaccine for avian influenza virus: a challenge study against highly pathogenic H5N2 subtype. Virology and antiviral research. Vol. 7: 1-5. 2018.2018.
5. Li, Jianping, Z. Helal, C. Karch, T. Girshick, A. Garmendia, N. Mishra, P. Burkhard and M. I. Khan. A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus. PLOS One, in press, September 6, 2018.
Natasha Lucki
Thermo Fisher Scientific, Inc., USA
Title: EXPISFâ„¢: A chemically-defined baculovirus-based expression system for vaccine production in Sf9 cells
Time : 17:00-17:30
Biography:
Natasha is a Product Manager at Thermo Fisher Scientific managing the insect and CHO protein expression product portfolios. Prior to joining Thermo Fisher, Natasha has completed postdoctoral research training in early-stage drug discovery at the California Institute for Biomedical Research in La Jolla, CA, USA and received a PhD in Cell & Molecular Biology from the Georgia Institute of Technology in Atlanta, GA, USA.
Abstract:
Baculovirus-insect cell expression system is one of the major platforms for recombinant protein production and a robust and versatile platform for vaccine production. Currently, eight commercially-available vaccine products and multiple vaccine candidates in development are produced in insect cells. Unlike mammalian expression systems that have long since transitioned to chemically defined culture media, relatively little innovation has taken place in insect expression systems. Insect cells continue to rely on undefined, yeastolate-containing culture media that can exhibit significant lot-to-lot performance variability and, therefore, negatively impact productivity. Here, we describe the ExpiSf™ Expression System, the first chemically defined insect expression system that enables high-yield production of proteins and viral particles with consistent performance run after run using a fast, streamlined workflow. This multi-component, optimized system delivers scalable yields from shake flask to bioreactor scale, thus facilitating vaccine development. The superior performance of ExpiSf provides researchers with the simplicity of obtaining high-titer recombinant baculovirus in one simple step and going from transfection to product harvest in 6-10 days
Wenping Gong
Institute for Tuberculosis Research, The 8th Medical Center of Chinese PLA General Hospital, China
Title: Evaluation of immunotherapeutic efficacy of vaccae vaccine and identification of differentially expressed genes in BALB/c mice infected with Mycobacterium tuberculosis
Time : 17:30-18:00
Biography:
Wenping Gong has his expertise in evaluation and passion in developing the novel tuberculosis vaccine (TB). His research focuses on the screening of specific epitopes and the construction of novel epitope vaccines. He has participated in many international academic conferences and delivered speeches. So far, he has published ten SCI papers in international academic journals. His work shed light on the prevention and treatment of the spread of TB, and opened new ideas for the development of new TB vaccines.
Abstract:
Background: Tuberculosis (TB) is the leading cause from a single infectious agent and one of the top 10 causes of death. Mycobacterium vaccae vaccine is the first preventive TB vaccine in phase III trials besides BCG. However, the differentially expressed (DE) genes of host infected with M. tuberculosis before and after M. vaccae vaccine treatment is still poorly understood.
Methods: In the present study, the immunotherapeutic efficacy of M. vaccae vaccine were assessed in BALB/c mice by weight measurement, colony formation units counting, organ coefficient evaluation, and histopathology. The total RNA was extracted from isolated peripheral blood mononuclear cells from BALB/c mice, and the DE genes were identified by microarray, and GO analysis and pathway analysis were performed.
Results: M. vaccae vaccine had a significant immunotherapeutic effect in mouse model, and 2,326 upregulated and 2,221 downregulated genes were identified to be DE genes in M. vaccae group compared with control group. Additionally, a total of 123 signaling pathways with significant differences were identified, and our speculation suggested that the upregulated and downregulated pathways most related to M. vaccae might be MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway.
Conclusion: Immunotherapeutic effect of M. vaccae might be enhanced via upregulating MyD88-dependent TLR signaling pathway and downregulating PI3K-Akt signaling pathway, which improved our understanding of the mechanism of M. vaccae vaccine immunotherapy.
Recent Publications
1. Gordon SV, Parish T. Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe. Microbiology (Reading, England) 2018;164(4):437-39 doi: 10.1099/mic.0.000601[published Online First: Epub Date]|.
2. Gong W, Liang Y, Wu X. The current status, challenges, and future developments of new tuberculosis vaccines. Hum Vaccin Immunother 2018;14(7):1697-716 doi: 10.1080/21645515.2018.1458806[published Online First: Epub Date]|.
3. Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV, Mosteller F. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. Jama 1994;271(9):698-702
4. Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995;346(8986):1339-45
5. WHO. Global tuberculosis report 2017. Geneva: World Health Organization, 2017:1-262.5.