Day 1 - Thursday, Nov 13, 2008

7:00

Registration & Breakfast

7:55

Chairman's Opening Remarks

[KEYNOTE PRESENTATION]

8:00

Adjuvant Systems for Vaccines Targeting Unmet Needs: From Concept To Clinical Evidence

Nathalie Garcon, PharmD, Ph.D.
Vice President
Head of Research
GSK Biologicals

Although vaccines have demonstrated their unparalleled impact on human health, there is still a need for vaccines adapted to specific populations (elderly, children, etc.) or against challenging diseases (malaria, avian influenza, HPV, cancer, etc.). To achieve the required enhanced, cross-protective, persistent, antigen-sparing or more targeted effector responses, Adjuvant Systems (AS) were developed. Tailor-made AS-antigen combinations improve protection via one or more of these mechanisms.
As are combinations of classical adjuvants (aluminium salts, oil-in-water emulsions, liposomes) with immunomodulators (MPL, QS21 or CpG). They are designed and evaluated preclinically and clinically to allow for the modulation of specific protective immune responses to the vaccines antigen(s). According to existing guidelines, safety is evaluated through the vaccine development from preclinical phase to post-licensure.
As are part of licensed vaccines [H5N1/AS03 prepandemic influenza, HBV/AS04 hepatitis B & HPV/AS04 cervical cancer], candidate vaccines [RTS,S/AS02 & RTS,S/AS01 malaria] and antigen-specific cancer immunotherapeutics (MAGE-A3/AS02 & MAGE-A3/AS15). AS specifically and selectively promote the recruitment of antigen-presenting cells and influence the pattern of cytokines produced during the interactions between the innate and adaptive immune systems. AS-antigen combinations not only induce higher antibody responses, but also selectively drive T-cell amplification & polarization and generate persistent cellular and humoral immune responses that are critical for enhancing protection against the targeted diseases. Overall, the AS adjuvanted vaccines are well tolerated with a favourable safety profile.
Although increased reactogenicity may be observed as compared to non-adjuvanted vaccines, this is mostly mild to moderate in intensity and transient in nature. No significant imbalances of medically important adverse events are noted and spontaneous reports are not indicative of any safety risk up to date.
Clinical studies of AS-containing vaccines will be presented that consistently demonstrated benefits such as enhanced vaccine efficacy and/or immunogenicity, sustained protection, antigen-sparing, cross-protection, while maintaining a favorable safety/reactogenicity profile in studied populations.

Session I: New Technologies in Vaccine Development

9:00

In Vitro Biomimetic Human Immune System Models: MIMIC System

William Warren, Ph.D., President & CEO, VaxDesign Corporation

The successful transfer between human biology and traditional test systems requires an intricate understanding of disease pathogenesis and cellular and humoral immunological responses at all levels; innate, adaptive, functional. This talk will provide data on the development of the in vitro MIMIC system to assess drug, biologics, vaccine and adjuvant candidates using tissue engineered constructs to mimic human immunophysiology. We will focus on the induction of (1) antigen-specific CD4 and CD8 T cell responses by examining both the quantity and the quality of the in vitro T cell responses, and (2) Ag-specific in vitro antibody generation to both recall and naïve Ags.
In the MIMIC model, we create an environment analogous to that within the secondary lymphoid tissues. The APCs trigger the differentiation of naive Ag-specific CD4+ and CD8+ T cells into helper and cytotoxic T lymphocytes, respectively, by measuring lymphoproliferation, effector function and intracellular cytokine production by these T cells. The MIMIC platform is much more sensitive than standard PBMC assays for eliciting helper T cell and humoral responses against soluble proteins and formulated viral vaccines. We will show that the in vitro MIMIC model reproduces the conditions that exist in vivo, such as the spatial segregation of immune cells and the temporal dynamics that bring different immune cells together in a sequential order that accurately reflects interactions in a lymph node.
Benefits for attendees include:
- Accurate and reproducible data
- High throughput: capacity for thousands of tests per month
- Captures genetic diversity
- Cost effective

9:30

Rational Design and Standardized Evaluation of Novel Genetic Vaccines

Charlotte Dalba, Ph.D., CEO, Epixis

Recombinant viral vectors and virus-like particles are considered some of the most promising vehicles to deliver antigens in prophylactic and therapeutic vaccines against infectious diseases and cancer. CompuVac’s main objectives were to setup 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.
We have now assembled and compared a unique set of vaccines of different classes, from viral vector derived vaccines to inert VLPs. We will present the results of such an evaluation and how it was translated into the development of an HCV vaccine.
The validated database and the tool box will be made freely available to the scientific community at the end of the project in June 2009.
CompuVac is a project financed by the European Commission, which involved 18 partners worldwide.

10:00

Networking and Refreshment Break

10:30

Synthetic Oligosaccharide-Based Bacterial Vaccines

Vince Pozsgay, Ph.D., Staff Scientist, NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Based on literature evidence and our own observations, it is likely that antibacterial human vaccines can be produced from oligosaccharides much smaller that the native bacterial polysaccharides. We surmise that improved vaccines can be constructed from chemically well-defined extended oligosaccharide fragments of bacterial capsular polysaccharides and O-specific polysaccharides. In the last twenty years chemical synthesis has advanced to the point where large oligosaccharides can be elaborated and covalently attached to immunogenic proteins. The talk will highlight important milestones towards synthetic, carbohydrate-based vaccines and will summarize the authors studies towards a chemically defined semisynthetic vaccine against the enteric pathogen Shigella dysenteriae type 1 that causes dysentery in many parts of the world.

Benefits of the proposed approach include:
- sidestepping the need to grow potentially dangerous bacteria as the source of the saccharide antigens
- easier analysis of the conjugate vaccines based on structurally well-defined oligosaccharides instead of large polysaccharides
-  improved mapping of the structural parameters influencing immunogenicity that may lead to improved conjugate vaccines

Session II: Vaccines for Infectious Diseases

11:00

Influenza Vaccines Incorporating Toll-Like Receptor Ligands

Alan Shaw, Ph.D., President & CEO, VaxInnate

The induction of an immune response to a pathogen is now known to rely upon the interaction of antigen presenting cells, T-cells and B-cells. Antigen presenting cells (APCs) pick up pathogens via a series of receptors that recognize pathogen associated molecular patterns (PAMPs). PAMPs are structures and motifs that are common elements of pathogens not found in higher order organisms. The Toll-Like Receptors (TLRs) are the best characterized of this series.
Historically, soluble proteins made by rDNA techniques have been poor immunogens. Two exceptions are the hepatitis B vaccines and the human papillomavirus vaccines, both of which are based on virus-like particles which bear arrays of immunological targets promoting uptake and processing by APCs.
We have shown that coupling a TLR ligand (a PAMP, flagellin, the ligand for TLR5) to an antigen dramatically improves its immunogenicity. Applying this principle to influenza vaccine antigens M2 and HA, we have induce potent immune responses in mice rabbits and humans. Given the simple nature of these PAMP-antigen fusions, they can be produced efficiently in prokaryotes at high yield with effective doses in the range of 1 ug.

Benefits of this system include:
• Rapid, simple production in a system amenable to tech transfer
• High yield, 400,000,000 doses from a single 1000L fermentation
• Rapid first dose seroconversion
• Quick turn-around of a new flu strain

[Oral Presentations from Outstanding Abstracts]

11:30

Lipid A Mimetics are Potent Adjuvants for an Intranasal Pneumonic Plague Vaccine

Scott A. Minnich, Ph.D., Department Microbiology, Molecular Biology, and Biochemistry, University of Idaho

An effective intranasal i.n. vaccine against pneumonic plague was developed. The formulation employed two synthetic lipid A mimetics as adjuvant combined with Yersinia pestis-derived V- and F1- protective antigens. The two nontoxic lipid A mimetics, classed as amino-alkyl glucosaminide 4-phosphates AGPs are potent ligands for the Toll-like receptor TLR 4. Using a murine BALB/c pneumonic plague model, we showed a single i.n. application of the vaccine provided 63% protection within 21 days against a Y. pestis CO92 100LD50 challenge. Protection reached 100% by 150 days. Using a homologous i.n. 1°/2° dose regimen, with the boost administered at varying times, 63% protection was achieved within 7 days and 100% protection was achieved by 21 days after the first immunization. Little or no protection was observed in animals that received antigens alone, and no protection was observed when the vaccine was administered to BALB/c TLR4 mutant mice. Vaccine-induced serum IgG titers to F1 and V-antigen were reflected in high titers for IgG1 and IgG2a, the latter reflecting a bias for a cell-mediated TH1 immune response. This intranasal vaccine showed 90% protection in Sprague-Dawley rats challenged with 1000 LD50. We conclude that lipid A mimetics are highly effective adjuvants for an i.n. plague vaccine.

11:45

Autologous Breast Cancer Vaccine Improves Host Lymphocyte Immunity (A Rationale For Immunotherapy)

Robert L Elliott, M.D., Ph.D., Elliott-Elliott-Head Breast Cancer Research and Treatment Centers

Introduction: Breast cancers are antigenic. The present study was initiated to determine if cancer cells could be prepared from patients to be used in whole cell therapeutic vaccines for immunotherapy to improve host immunity.
Methods: We began preparing autologous whole cell preparations in 1995. The goal was to obtain one million cells per vaccine for six vaccines, and if there were too few cells, attempt to expand the cells in culture. The preparations were used in lymphocyte blastogenesis assays (LBAs) before and after vaccination to access each patient's immunity.
Results: Autologous whole cell preparations were obtained from 104 patients. Seventeen percent of the tumor digests contained no cells. In 18% of the patients the tumor digests yielded 0.5 million cells, and in 65% of the patients the digests produced 1 million cells for an autologous vaccine. In 65 patients, the tumor digests produced enough cells for two LBAs and six vaccines (patients had three weekly and three monthly intradermal injections). Ten weeks after the last injection, a repeat LBA was performed.
Conclusions: Depressed host lymphocyte immunity in a LBA is an unfavorable prognostic indicator in breast cancer and the conventional therapies of surgery, chemotherapy and radiation are immunosuppressive. When our vaccine was given to patients with depressed immunity after completion of conventional therapy, it restored specific lymphocyte immunity in the majority of the vaccinated patients. Also, some dramatic responses have been seen in Stage IV patients using combination chemoimmunotherapy. The results of patients vaccinated in the adjuvant setting are being evaluated and strongly suggest a marked improvement in disease-free survival. The time for breast cancer immunotherapy is now.

12:00

Lunch

1:00

A Comprehensive Mucosal Vaccine Approach for Protection Against HIV

Marjorie Guroff, Ph.D., Head, Immune Biology of Retroviral Infection Section, NIH/NCI

Vector prime/protein boost strategies based on replicating adenovirus (Ad)-HIV recombinants have been shown to elicit better cellular immunity and prime higher titer antibodies with functional activities compared to non-replicating Ad-HIV vaccines. Further, in the SIV-rhesus macaque system, the replicating Ad-SIV/envelope protein boost approach has elicited potent, durable protection against virulent SIV mucosal challenge. Discussion of recent pre-clinical vaccine studies will illustrate the elicitation of cellular and humoral mucosal immune responses using such a vaccine strategy. Importantly, the research findings emphasize the need to develop highly sensitive assays for cellular mucosal immunity that can be applied to easily sampled peripheral blood samples rather than mucosal tissues. Evaluation and elicitation of functional mucosal antibody responses will also be discussed. Development of a successful HIV vaccine will depend on induction of strong mucosal immune responses. The ability to detect and quantify such immune responses in future clinical trials will be critical to the on-going design and optimization of vaccines for HIV/AIDS.
The session will cover the following:
1. The benefits to use of replication competent Ad-recombinants as vectors for mucosal vaccines
2. State-of-the art techniques for evaluation of cellular mucosal immunity, and their limitations
3. Sensitive assays for broad-spectrum functional antibodies in sera and secretions that span innate and adaptive immunity
4. Elucidation of “correlates of immune protection” in the SIV rhesus macaque system that may mimic protection in humans against HIV

1:30

Early Development of a Broadly Protective Meningitis Vaccine Based on Heat Shock Protein Antigen Complexes

Christopher Bailey, Ph.D., Development Director, ImmunoBiology Ltd

There is an urgent need for a vaccine against Neisseria meningitidis serogroup B strains. Although B vaccines have been produced in response to specific epidemics, they are not broadly protective and other approaches are required. This presentation will describe the application of a novel vaccine technology to address this demand.
Heat shock proteins are multifunctional. As chaperones, heat shock proteins facilitate the folding and unfolding of proteins in the cell and therefore are always found complexed to other protein cargos. In the context of infectious diseases, these heat shock protein antigen complexes (HspCs) from the pathogen are critical to immunity, bridging between the innate response and the induction of specific responses to the cargo antigens including cross-presentation on MHC class 1 molecules on antigen presenting cells (APCs).

Benefits of ImmunoBiology’s HspC vaccine approach:
- Efficient (specific uptake of HspCs by APCs)
- Low dose levels (no adjuvant)
- Broad Response (full set of pathogen’s antigens, no MHC restriction)
- Safety (not live, no adjuvant)

HspC based vaccine has been produced from heat shocked pathogen Neisseria meningitidis using chromatographic methods. The ability of this vaccine to induce broad responses in mice has been demonstrated by serum opsonophagocytosis activity against a panel of Neisseria strains.

2:00

Vaccination Strategies for Adenovector-Based Malaria Vaccine

Katarina Radoševic, Ph.D., Vice President Immunology and Proof of Concept, Crucell

Annually more than 500 million people become severely ill with malaria and many of them die, especially children in sub-Saharan Africa. Currently available protective measures, such as insecticide spraying and bed nets, are not sufficient to control spread of the disease. At present there is no malaria vaccine available. Among different vaccine technologies, replication-deficient rare serotype adenoviral vectors are very promising, due to the ability to induce strong immune responses and their safety. In addition, availability of highly efficient manufacturing platforms, such as PER.C6? cell line, which is able to fulfill the global vaccine demand, makes adenovectors very attractive as a vaccine vehicles. In this presentation different strategies to further enhance immunogenicity and protective ability of Ad35-based malaria vaccine will be discussed.

Benefits of this presentation:
- Advantages of adenovector-based vaccines
- Rare adenovector serotypes
- Antigen selection
- Prime-boost immunization regimens
- Route of immunization

2:30

Networking and Refreshment Break

Session III: Vaccines for Non-Infectious Diseases

3:00

Development of a Nicotine Vaccine

Erich Cerny, MD, Chief Scientific Officer, Chilka LTD

Nicotine by itself is too small a molecule in order to elicit antibodies after inhalation. But it can be linked to a large carrier molecule to render it visible to the immune system of a smoker. The anti nicotine vaccine uses such a nicotine carrier molecule conjugate in order to elicit antibodies against nicotine. Antibodies appear 2 to 3 weeks after the start of the vaccination procedure. The nicotine entering the body through the lungs gets bound to the anti-nicotine antibodies circulating in the blood stream. The antibody nicotine complex is too big to cross the blood brain barrier and the large antibody molecule bound to the small nicotine molecule interferes with the interaction of the nicotine with specific receptors.
The anti-nicotine vaccine cuts the vicious circle between smoking and nicotine stimulation by diminishing significantly the immediate nicotine stimulation of inhaled cigarette smoke. The anti-nicotine vaccine has on the other hand no direct effect on the craving of a smoker for nicotine. Nicotine vaccines are a complement to existing smoking cessation treatments and need professional counseling in order to achieve maximal efficiency.
Benefits to attendees:
- The basic science of nicotine vaccines is discussed
- Data of different application forms of the vaccine in animal models are presented
- An up-to-date compilation of published preclinical and clinical data of anti nicotine vaccines is established
- Nicotine vaccines are compared with classical treatments for smoking cessation

3:30

A New LEAPS Therapeutic Vaccine for Rheumatoid Arthritis: Arising from Work on Earlier LEAPS Vaccine

We have used the well established DBA/1J Collagen Induced Arthritis (CIA) model and compared the results obtained with vaccinations with CEL-2000 to treatments of Enbrel. We have shown our LEAPS therapeutic vaccine is equivalent or superior to Enbrel in slowing disease progression and lessening arthritis symptom in mice. During a 28 day period either two CEL-2000 vaccinations or 14 treatments of Enbrel were administered to groups of 8 mice after they had developed significant Al mean scores. Data for both Arthritis Index scores and hind foot paw thickness will be presented for both treatments. Serological results of antibodies, isotypes and specificity obtained in this study will also be presented. This work arose from previous studies of other LEAPS vaccines evaluated in model of experimental autoimmune myocarditis and infectious diseases for HSV and HIV. These studies included a vaccine antigen that will be considered as a potential clinical candidate depending on the results of ongoing formulation, delivery, and mechanism of action studies. CEL-2000 is antigen specific acting on the cause of the disease. It acts by a completely different mechanism from Enbrel and other cytokine soluble receptors or monoclonal antibodies which act on the cytokines induced during the disease process many of which are essential for other normal immune functions to protect infection.

Benefits for attendees:
- May be used in conjunction with other therapies
- Potentially less doses and toxic
- Fewer doses and spread further apart
- Acts by different mechanism than current therapies
- Avoids removing or tying up TNF-a

4:00

The Use of Antibody Targeted HLA Complexes as Vaccines and for Optimizing Elispot Analysis of T cell Responses to any HLA Class I/II Peptide Combination

Recombinant HLA class I/II-peptide complexes bound to the surface of a target cell via an antibody remain functional and can effectively interact with T cells of the appropriate specificity. We have demonstrated that this technology can be used in animal models to re-direct virus specific cells to kill tumour cells and alternatively when bound to healthy B cells can be used to expand therapeutically useful T cells. We will describe how this simple and robust technology may be useful for expanding oligoclonal T cell populations in patients for the treatment of malignancies and serious viral infections.
In vitro the same simple technology can be used to expand T cells for analysis with similar levels of efficacy as the use of dendritic cells. Combining this technology with the use of HLA class I and class II negative target cells allows the production of target cells/APCs of a single chosen immunological identity. These cells should offer an advantage in assaying T cell activity by functional analysis methods including; Elispot, intra-cellular cytokine production and functional killing assays. These cells termed HLA mono-specific cells are simple and cheap to produce, highly reproducible and only require a single target cell to be kept in culture to test T cell activity against any chosen HLA allele/peptide combination. The data presented will show how assays can be simply performed testing for HLA-A2/peptide combinations, any non-HLA-A2 HLA class I combination and any chosen HLA class II/peptide combination all using the same base cell.
Other groups wishing to explore the use of this system in their own immunotherapy research are welcome to share the resources and experiences in this new technology.

4:30

Poster Session & Networking Reception

Day 2 - Friday, Nov 14, 2008

Top of the page

7:00

Continental Breakfast

7:55

Chairman's Review of Day One

[KEYNOTE PRESENTATION]

8:00

The Office of Vaccines Regulatory Updates

Norman Baylor, Ph.D.
Director
Office of Vaccines
FDA

The Office of Vaccines Research and Review in the FDA’s Center for Biologics Evaluation and Research is responsible for the regulation of vaccines, allergenic extracts, and related products licensed in the U.S. New manufacturing methods and technologies for developing new and/or improved vaccines, such as cell-culture based influenza vaccines, as well as the use of novel adjuvants present unique challenges to National Regulatory Authorities including the U.S. FDA. The FDA must be in a position to develop new scientific and regulatory criteria to evaluate vaccines produced from new technological advances. Other challenges the FDA encounters include how to facilitate the development of new vaccines targeted for special populations as well as developing regulatory pathways for the evaluation of vaccines against diseases that are not endemic in the U.S. There are also challenges evaluating the manufacturing as well as the clinical outcomes of vaccines made with these new technologies. Can these technologies be scaled-up, are the resulting products manufactured consistently from lot to lot; are they stable? What endpoints do we use to evaluate these vaccines in the clinic for safety and efficacy? Are there special safety concerns that must be considered when evaluating the risk versus benefit of these new vaccines? OVRR/CBER is in a unique position to address these issues from a research and regulatory review perspective.
Some of the major vaccine initiatives in the Agency include pandemic and emerging infectious disease preparedness, enhancing product safety, global engagement and leadership, and implementation of the Food and Drug Administration Amendments Act (FDAAA).
There are many challenges facing the FDA in the world of public health and vaccine development. We are committed to ensuring the safety and effectiveness of vaccines and related products. FDA’s Office of Vaccines Research and Review is engaged in a leadership role to prepare for and respond to the risks of emerging diseases such as pandemic influenza, malaria, tuberculosis, HIV and other infectious diseases. The OVRR is optimizing the vaccine regulatory review and licensing processes (e.g., accelerated approval, fast track, priority review, and use of the “animal rule”) to encourage new vaccine development and make vaccines available sooner. We have made significant strides in aiding vaccine manufacturers, and facilitating the development of new vaccines such as rotavirus, zoster and HPV.

Session IV: Regulatory & Government Policy

[FEATURED PRESENTATION]

9:00

Secrets of NIH SBIR and STTR Grant Applications

Gregory Milman, Ph.D.
Director
Office of Innovation
NIAID / NIH

When the going (funding) gets tough, the tough go shopping (for grants and contracts). As NIH success rates enter single digits and venture capital funding diminishes, academic investigators and small companies collaborate to apply for NIH Small Business Funds (SBIR & STTR).

Attend this session of the 6th Annual Vaccines Conference to hear funding secrets of the $750 million NIH SBIR and STTR programs. Learn:
* How to decide between SBIR or STTR programs
* What is flexible and what is not in SBIR and STTR eligibility rules
* Success rates for NIH applications
* Strategies for producing winning proposals
* How to receive more than the "Normal" amount of funds
* NIH Material Transfer Agreements, Licenses, and Cooperative Research and Development Agreements
* NIH Pipeline to Partnerships (P2P)
* NIH SBIR/STTR Collaboration Opportunities and Research Partnerships (CORP)
* NIH SBIR Technical Assistance Programs

Attending this session could be time well-spent if it helps you obtain funding.

10:00

The National Vaccine Plan: A Vision for the United States

Raymond Strikas, Medical Advisor, HHS, National Vaccines Program Office

The first National Vaccine Plan was published in 1994. The National Vaccine Program
Office (NVPO), part of the Department of Health and Human Services (HHS), is updating the Plan. The National Vaccine Program Director [the Assistant Secretary of Health] is required to coordinate and provide direction (plan) for vaccine activities, including research and development, safety and efficacy testing, licensing, production and procurement, distribution and use, evaluating effectiveness and adverse effects, governmental and nongovernmental activities, and federal funding. NVPO, with HHS offices and agencies, the Departments of Veterans Affairs and Defense, and the U.S. Agency for International Development, has drafted priorities for the updated Plan. These priorities have been reviewed with the National Vaccine Advisory Committee, and with an Institute of Medicine (IOM) expert committee. The IOM committee is discussing these priorities with stakeholders, and will report to NVPO. NVPO will also solicit input about the Plan from a sample of the general public. The Plan should be completed in 2009. The Plan's priorities include basic and applied research, vaccine safety and compensation, vaccine supply and financing, childhood, adolescent, and adult immunization, vaccines for preparedness and improving global health, communication and education, and surveillance of disease and vaccine uptake. The updated National Vaccine Plan will reflect changes in vaccines since 1994, and offer direction for priorities and accountability in the prevention of infectious diseases by vaccination.

Attendees at this talk will learn:
1. An updated National Vaccine Plan is being created.
2. Stakeholder input is necessary and welcome.
3. Input can be given to both the IOM and NVPO.
4. The Plan should be completed by late 2009.

10:30

Networking an Refreshment Break

11:00

Public-Private Partnerships in Vaccine Development

Frank Rapoport, Esq., Partner, McKenna Long & Aldridge LLP

Vaccines provide tremendous public health and preparedness value. However, while there is a need for novel vaccines to address unmet needs and improve health care, the development of novel vaccines can be costly and risky. To help reduce the investment risk and facilitate the development of needed products, companies can leverage development through numerous public-private partnerships. These include programs through the National Institutes of Health (NIH), the Department of Defense (DOD), the Biomedical Advanced Research and development Authority (BARDA) in HHS, and various NGOs. In order to compete successfully for partnership opportunities, product developers must understand the various roles and priorities. This discussion will explore these partnerships and the potential for vaccine developers to seek undiluted financing to advance technology platforms and advance towards commercialization.

Objectives:
- Highlight opportunities to advance vaccine development through public-private partnerships
- Understand the priorities and roles of various partnerships
- Explore potential future directions in public-private partnerships

11:30

Vaccine Innovation: The Government Potential to Impact the Risk Reward Equation

Angela Shen, Ph.D., International Policy Analyst-Vaccine Specialist, National Vaccine Program Office, HHS

Vaccine innovation occurs in stages, within the context of the US health care system, and with the involvement of many stakeholders. The key to innovation extends beyond development and licensure of a vaccine to the delivery of the vaccine into the patient, payment to the provider, and reimbursement by the payor for the vaccination. The development of vaccines is influenced by many of these elements and the potential for the government to influence the development of a vaccine is contingent on understanding how these elements are inter-related.

Session V: Future Trends in Vaccine Discovery

12:00

Potential of M Cell-Targeted Delivery of Mucosal Vaccines and Immunotherapeutics

Wangxue Chen, Ph.D., Senior Research Scientist, National Research Council Canada, Institute for Biological Sciences

M (microfold or membranous) cells are specialized epithelial cells responsible for antigen sampling at the interface of mucosal surfaces and the environment. Their high transcytotic ability make M cells an attractive target for mucosally delivered vaccines and therapeutics. A variety of synthetic microparticles / nanoparticles have been developed and tested as vehicles for M cell targeted mucosal drug and vaccine delivery. b1 integrins, pathogen recognition receptors, specific carbohydrate residues and other M cell surface antigens have been exploited as potential targets for the delivery of mucosal vaccines and therapeutics. However, much work still needs to be done before an effective M cell-targeted mucosal vaccine or therapeutic is developed. In this presentation, the current state of M cell targeted mucosal delivery systems and the potential of such delivery systems for the development of new vaccines and therapeutics against mucosal infectious and inflammatory diseases will be summarized and discussed.
• What is the importance of mucosal infection and inflammation?
• What are the current approaches in the mucosal vaccine development?
• Why deliver vaccines and drugs through mucosal route?
• What is the advantage of M cell targeting approach for mucosal vaccine and drug delivery?
• What are the challenges in M cell targeted mucosal vaccine and drug delivery?

12:30

Luncheon

1:30

Vital Steps for Successful Immune Monitoring Strategies to Accelerate Time to Market for Novel Vaccines and Therapeutics

Thomas Kleen, Ph.D., Director of Business and Technology Development, Cellular Technology Limited

There are vital steps and considerations for the successful design and execution of pre-clinical and clinical trials that deliver regulatory acceptable data. In this context the inclusion of immune monitoring strategies can initially appear challenging, resource consuming, and costly; however, there has been a growing appreciation in the field of the broad possible benefits of immune monitoring strategies. Performed correctly immune monitoring has the potential to accelerate time to market for novel vaccines, for which it can be challenging to obtain clinical endpoints in a timely fashion. Several regulatory agencies, including the U.S. Food & Drug Administration (FDA), recently emphasized the need for better prognostic models and the establishment of correlates of protection or relevant biomarkers for novel vaccines that aim to elicit cellular immunity. Immunologic monitoring, therefore, has been established as an advisable adjunct to clinical trials with biologic agents including vaccines. Linking correlative immunologic studies with clinical endpoints successfully requires extensive scientific expertise, laboratory support and their performance under defined quality assurance (QA) and quality control (QC) conditions. If executed correctly in good laboratory practice (GLP) facilities with the capability of performing standardized high-throughput assays, immune monitoring strategies can have large net present value (NPV) and product lifecycle benefits to the Sponsor through an accelerated approval of a novel vaccine. The intellectual property (IP) protection for vaccine principles and platforms is limited. The ability to enter the market early or to quickly refocus on alternative approaches (due to a lack of advocacy of candidate vaccines), can add weeks, months or even years to a products lifecycle under IP protection.
Benefits:
• Highlights how early detecting of relevant responses requires a careful choice of test systems and cytokines to be monitored.
• Elaborates how highly sensitive, validated GLP compliant ELISPOT assays significantly aid the progress of new vaccines through the pipeline by providing crucial immunogenicity and safety relevant information.
• Explains how standardization of specimen processing, cryopreservation and sample management are vital steps for successful immune monitoring strategies during multicenter clinical trials

2:00

Engineering New Vaccines with Actively Targeted Biodegradable Nanoparticles

Tarek Fahmy, Ph.D., Assistant Professor, Biomedical and Chemical Engineering, Yale University

Pathogens are continually emerging and changing; therefore, there is a constant need for
desiging and screening new vaccine systems. Here we present a new class of nanomaterials endowed with properties that allow for rapid optimization of vaccine design. We constructed a generalizable vaccine delivery system using a simple approach that tethers dendritic cell ligands to the surface of nanoparticles constructed from biocompatible polyester, poly (lactic-co-glycolic acid)
(PLGA) and loaded with a model antigen, ovalbumin. We show that surface-modified nanoparticles were preferentially internalized by dendritic cells compared to uncoated nanoparticles. We further demonstrate that the system elicits both humoral and cellular protective immunity after subcutaneous as well as oral administration in a model of West Nile Infection.

2:30

The Evolving Vaccine Marketplace: Drivers for Development and Innovation

Chris Colwell, Ph.D., Senior Advisroy, McKenna Long & Aldridge LLP

The vaccine market place, both domestically and globally, has grown significantly in the past several years and many project continued substantial growth. There have been several factors driving this growth, including increasing returns on investment relative to competing investments, increased demand for adult vaccines, pandemic and public health preparedness, and an increasing health infrastructure in developing nations. This increased demand is driving investment in vaccine innovations along several dimensions – such as new antigens, new manufacturing technologies, new adjuvants, and new delivery systems. However, there are challenges for continued innovation, and successful developments must not only be scientifically sound, but provide added value and efficiencies in the clinical setting and address unmet needs in a cost-effective manner. New products in development should consider supply chain efficiencies, how product will be delivered and reimbursed in the clinical setting, and the needs of targeted domestic and international populations. This discussion will explore these factors and drivers, and identify challenges and opportunities for continued growth of the vaccine market.

Objectives:
- Highlight the increasing domestic and global market for vaccines
- Explore future potential demand drivers for innovations in new disease areas and technologies
- Explore potential barriers and opportunities to overcome them

3:00

Conference Concludes