Thursday, August 14
Development: Transforming Concept into Product
7:30am Registration and Morning Coffee
(Breakfast Workshop Sponsorship Available)
IN SUPPORT OF VACCINE DEVELOPMENT
8:30 Chairperson’s Remarks
Sudaxshina Murdan, Ph.D., Senior Lecturer, Pharmaceutics, Fellow, Higher Education Academy, The School of Pharmacy, University of London
8:35 Rational Design and Standardized Evaluation of Novel Genetic Vaccines
David Klatzmann, M.D., Ph.D., President, European Society for Gene Therapy
Recombinant viral vectors and virus-like particles are considered one of the most promising vehicles to deliver antigens in prophylactic and therapeutic vaccines against infectious diseases and cancer. CompuVac is a project financed by the European Commission, which involves 18 partners worldwide. CompuVac’s main objectives are to set up a standardised approach for the rational development of genetic vaccines and to apply this methodology to the development of vaccines against the hepatitis C virus.
The process comprises the development of: (i) a large panel of vaccine vectors representing various vector platforms and all expressing the same model antigens; (ii) standardized methodologies for the evaluation of T- and B-cell responses and of molecular signatures relevant to safety and efficacy; (iii) a database for data storage and analysis of large data sets; (iv) intelligent algorithms for the rational development of prime boost vaccination. One of our final goals is to generate and make available to the scientific community a “tool box” and an “interactive database” allowing the comparative assessment of future vaccines. We also aim to validate these tools by the rational development of preventive and/or therapeutic vaccines against HCV. We have now assembled a unique set of vaccines of different class, from viral vector derived vaccines to inert VLPs, analysed their efficacy with standardised methodologies, and compared them with an intelligent database. This has already allowed us to make significant comparisons between different vaccine types and to initiate novel vaccine design and vaccination regimen. We are now evaluating prime-boost immunisation regimens with these vectors. We believe that this should have a significant impact on vaccine development, and notably for those vaccines requiring prime/boost immunizations.
9:05 An Ontology-Based Information Network to Support Vaccine Research
Yongqun Oliver He, D.V.M., Ph.D., Assistant Professor, Unit for Laboratory Animal Medicine and Department of Microbiology and Immunology and Center for Computational Medicine and Biology and Comprehensive Cancer Center, University of Michigan Medical School
Since the introduction of Edward Jenner’s cowpox-based vaccine against smallpox in 1796, vaccines have proven invaluable for their ability to stimulate the immune system and to confer protection against pathogenic microorganisms. Vaccine research and development have undergone a renaissance that is in part attributable to the cost-effectiveness of vaccines and to advanced post-genomic technologies. As progress in vaccine research has been accompanied by a dramatic increase in the number of vaccine-related papers, it has become increasingly challenging to retrieve vaccine data from literature in a targeted way, which will allow the data retrieved to be used for analysis and for the testing of hypotheses. There exists, accordingly, an ever increasing need for a means to store, annotate, compare, and analyze vaccine information as this relates to different pathogens and different hosts. Although vaccine databases exist that emphasize commercialized vaccines, no public central repository is available which makes research data concerning either commercial vaccines, those vaccines in clinical trials or those in early stages of development, available for analysis. To fill this need, we have developed VIOLIN, a web-based database system for annotation, storage, and analysis of published vaccine data
(http://www.violinet.org). VIOLIN addresses a further bottleneck of vaccine research, which is the lack of a Vaccine Ontology, a controlled, structured vocabulary for vaccine data standardization, integration, and analysis. We believe that our collaborative approach and novel methodology will establish VIOLIN as a web-based vaccine resource center for vaccine data integration, annotation, standardization, storage, query, and analysis.
9:35 Technologies for Improved Vaccines
Jeffrey B Ulmer, Ph.D., Senior Director, Vaccines Research, Novartis Vaccines & Diagnostics Inc.
This talk will address the technical gaps in the vaccines discovery and development process, along with current breakthrough solutions including:
- antigen discovery and optimization
- novel vaccine delivery systems
- novel vaccine adjuvants
10:05 Coffee Break in the Exhibit Hall
INNOVATING VACCINE DEVELOPMENT
10:45 Innovative Influenza Virus-Like Particles Provides Protection Against an H5N1 Challenge
Manon Couture, Ph.D., Project Leader, Product Development and Innovation, Medicago Inc.
Medicago recently adapted its proprietary transient expression technology to the production of influenza antigens in plant biomass. It is the first demonstration that plants can produce influenza virus-like particles (VLPs), which bud from the plasma membrane and contain plasma membrane constituents. In contrast to other production systems, the formation of VLPs structures can be obtained from the sole expression of the hemagglutinin antigens. Results will be presented that show the efficacy of these influenza VLPs to protect against lethal challenges with pandemic strains. These results demonstrate the potential of our technology for fast response, dose-sparing and critical surge capacity in an efficient and cost-effective manner in the event of a pandemic outbreak.
11:15 SPR Technology as a Powerful Tool to Accurately Determine Influenza Virus Concentration
Camilla Estmer Nilsson, PhD, Scientist, Life Sciences, GE Healthcare Bio-Sciences AB, Sweden
Determining influenza virus hemagglutinin (HA) concentration is critical for the final formulation of the vaccine and for manufacturing process development. The HA concentration is commonly determined by single radial immuno-diffusion assay (SRID) as recommended by the European Pharmacopoeia and WHO. However, the SRID assay has a number of disadvantages as it is laborious and has a low detection range inducing high variation. Thus, SRID is not an optimal method for either batch release analysis of the vaccine or in process development. Surface Plasmon Resonance (SPR) technology monitors the interactions of a molecule on the surface of a chip, and holds the potential of being a highly sensitive, less time-consuming and more accurate methodology. In this study, an analytical method using Biacore™ was developed with the goal of receiving a robust and accurate assay for three influenza virus types (A/H1N1, A/H3N2 and B) with a lower detection limit than SRID. Furthermore, the assay was shown to have higher precision for in-process samples and a higher detection range with a limit of detection ~1 log lower than SRID. Therefore, the Biacore assay is among the most compelling analytical tools in process development for influenza vaccines.
11:45 Preclinical Development of dl5-29, a Replication-Defective Vaccine Against Genital Herpes
Simon Delagrave, Ph.D., Director, Biotherapeutics Research and Leader, the Herpes Vaccine Project, Acambis
Human herpes simplex virus type 2 (HSV-2) is a double stranded DNA virus of the Herpesviridae family. Nearly 20% of the population in the USA is infected with this virus which is the primary cause of genital herpes and a significant risk factor for HIV-1 infection. Disseminated HSV-2 infection can be lethal in newborns and the immuno compromised. The significant economic burden and medical need caused by this disease provide a powerful rationale for a vaccine against HSV-2. This presentation will discuss the preclinical development of dl5-29, a replication-defective HSV-2 virus. This vaccine candidate was shown to protect mice and guinea pigs against challenge with wildtype HSV-2, and to be more immunogenic than gD2, the antigen currently in clinical development as a subunit vaccine. The immune response to purified dl5-29, both in terms of T cell responses, as well as proliferative responses, serum IgG responses, and cytokine expression, will be discussed. Our data set a clear path for clinical development of this promising vaccine.
12:15pm Networking Luncheon (Riverfront Room)
PLENARY SESSION – FOCUS ON ADJUVANTS
1:40 Chairperson’s Remarks
William Egan, Ph.D., Executive Director, PharmaNet Consulting
1:50 Plenary Keynote Presentation
A CBER Perspective on the Use of Novel Adjuvants in Vaccines: Challenges and Opportunities
Norman W. Baylor, Ph.D., Director, Office of Vaccines, CBER, FDA
KEYNOTE PRESENTATION
 2:30 Unique Vaccine Adjuvant Efficacy of Toll-like Receptor 8 (TLR8) Agonists that Activate Human Antigen-Presenting Cells
Ofer Levy, M.D., Ph.D., Staff Physician, Infectious Diseases and Principal Investigator, Harvard Medical School/Children’s Hospital Boston
Activation of antigen-presenting cells is a key feature of effective vaccine adjuvants. Our group has discovered that uniquely among the many TLR agonists, a novel family of compounds called imidazoquinolines that activate cells via TLR8 can effectively activate antigen-presenting cells from human newborn cord blood, inducing production of Th1-polarizing cytokines (TNF, IL-12) and upregulation of co-stimulatory molecules (CD40). These observations suggest that these agents may have unique vaccine adjuvant activity in infants and newborns |
FEATURED PRESENTATION
3:00 CpG TLR9 Agonists as Adjuvants for Prophylactic and Therapeutic Vaccines
Heather Davis, Ph.D., Senior Vice President, Vaccines Research Site Head, Ottawa Research Laboratories, Coley Pharmaceutical Group, a Pfizer company
Oligodeoxynucleotides containing CpG motifs are activate innate immunity through Toll-like Receptor 9 (TLR9), and when combined with antigens act as potent adjuvants to augment both humoral and cell-mediated responses. This talk will review animal and human clinical data testing CpG ODN with a variety of antigens.
3:30 Artificial Cells Derived from Biodegradable Materials that Boost the Immune Response
Tarek Fahmy, Ph.D., Assistant Professor, Biomedical Engineering, Yale University
While dendritic cells (DCs) are the most potent professional antigen-presenting cells, their widespread utility in therapeutic approaches involving ex vivo stimulation of T lymphocytes is hindered by several practical factors such as generation of autologous DCs, labor and isolation and preparation for clinical applications. Thus, artificial antigen-presenting cells (aAPC) have been proposed and tested in the expansion of a number of specific T cells for the treatment of a variety of disease states. Here we have developed a novel physiologically compatible system of “cell-like” particles for ex vivo and in vivo T cell stimulation using biodegradable polymers. Our approach fabricates FDA approved polymers into particles presenting T cell antigens, thus providing the multivalent interactions necessary for efficient stimulation of T cells. A key feature of this technology is the ability to co-encapsulate cytokines and program their release during and after activation and in a sustained fashion, facilitating long-term bioavailability and efficient stimulation of lymphocytes.
4:00 Refreshment Break in the Exhibit Hall (Last chance for viewing)
4:45 From “Alchemy” to Agonists of the Innate Immune System - Features and Applications of the Next Generation Vaccine Adjutants
Benjamin Wizel, Ph.D., Head, Preclinical R&D, Intercell AG
Several decades ago, adjuvants have entered the vaccine arena in order to facilitate the built-up of protective immunity by vaccines. Up till now only a few adjuvants have been formulated into registered vaccine products; mostly the salts of aluminum. The mode of action of the existing adjuvants is not well understood. Aside of their protection of the antigens against degradation and depot formation at the injection site, it’s very little known, how they kick off the immune cascade. The discovery of the Toll-like receptors on the surface of dendritic cells that are able to binding to so-called Pathogen Associated Molecular Signals, PAMS, has opened a new target to design specific adjuvants that not only induce antibodies, but also cellular immunity, thereby broadening the specificity and the quantity of immune responses towards vaccine antigens. At Intercell, we have developed a novel adjuvant, IC31, comprising an antibacterial peptide and a Toll-like 9 agonist that is mixed together with the vaccine antigens. I will discuss in my presentation profile and mode of action of IC31 and the promising results obtained when the adjuvant was tested in a variety preclinical and clinical settings.
5:15 The Use of SCV-07, a Novel Immune-Stimulating Dipeptide, as an Enhancer for Vaccines
Cynthia Tuthill, Ph.D., Senior Vice President and Chief Scientific Officer, SciClone Pharmaceuticals
SCV-07, or γ-D-glutamyl-L-tryptophan, is being evaluated for therapeutic use in a number of immune-compromised conditions, including hepatitis C, mucositis, and certain cancers. The immune-stimulating effects of SCV-07 treatment, including polarization of the immune response towards the Th1 profile, suggest that SCV-07 could also be useful for enhancement of responses to certain vaccines. This talk will focus on recent data from animal models which have demonstrated improved responses to various vaccines, including those for influenza, tuberculosis, and breast cancer.
5:45 Nanoemulsion-Based Vaccines are Safe Adjuvants that Deliver Antigens to Mucosal Surfaces
Joyce Sutcliffe, Ph.D., Vice President, Research, NanoBio Corporation
Nanoemulsion-based vaccines employ oil-in-water emulsions composed of nanodroplets with an average diameter of 400 nm. The nanodroplets can inactivate whole viruses or bacteria, incorporating native-like antigenic components into their structure. Alternatively, purified antigens can be mixed with the nanoemulsion adjuvant for delivery to mucosal surfaces. The composition and particle size of the nanodroplets are designed for preferential uptake by dendritic cells. Antigen processing triggers maturation of the dendritic cells and trafficking to secondary lymphoid tissues. A robust response to nanoemulsion-based vaccines has been shown for multiple antigens and intranasal administration of these vaccines in several animal models has occurred without signs of toxicity to the mucosal structure or local irritation.
6:00 Refreshment & Appetizer Break
6:15 Interactive Panel Discussion with Plenary Speakers (Grand Ballroom B)
Please join in the extended discussion of Adjuvants
Moderated by William Egan, Ph.D., Executive Director, PharmaNet Consulting
7:15 End of Day Two, Novel Vaccines; Close of Conference, Advances
End of Day Two