Thursday, August 23 - Day Two
Development: Transforming Concept into Product

7:30 am Morning Coffee (Breakfast Workshop Sponsorship Available)

Promising Developments
Using Epitopes

8:30 Chairperson's Remarks

8:35 Use of “Mixed Delivery Format” Epitope-Based Vaccines to Appropriately Direct Cellular Immune Responses
Glenn Ishioka, Ph.D., Director of Vaccine Immunology, Pharmexa Epimmune
Cellular immune responses associated with control and clearance of complex intracellular pathogens are generally composed of both CD4+ Helper (HTL) and CD8+ Cytotoxic T-lymphocytes (CTL). The specificities of HTL and CTL are determined through the epitopes recognized but the characteristics of their epitopes differ and they are generated through different cellular pathways. The use of simple or single component vaccines can therefore lead to the induction of suboptimal immune responses. However the use of different vaccine formats may prove useful as a means to compensate. To address this issue, we evaluated immune responses induced using individual HTL and CTL epitopes in the form of peptides, recombinant proteins composed of epitopes and epitopes encoded by genetic vaccines (DNA plasmids and viral vectors) to determine which were most effective for inducing and boosting immune responses. All of the tested vaccine delivery formats were effective for inducing HTL responses whereas DNA plasmid based vaccines appeared most effective for priming CTL responses which were boosted using peptides and viral vectors. The combined use of different vaccine delivery formats significantly increased the magnitude of CTL responses whereas HTL responses are not boosted to a lesser degree. The synergistic effects of different vaccine delivery formats appears to be related primarily to dose of epitope delivered although the combined use of cross-priming and direct epitope presentation by professional antigen presenting cells also contributes to increase magnitude of CTL responses.

9:05 A Novel Strategy to Mimic Discontinuous Protective Epitopes Using a Synthetic Scaffold
Robert Liskamp, Ph.D., Professor, Pharmaceutical Sciences and Chemistry, Utrecht University
Although vaccines have been used for a long time and different types of vaccines have been developed, as yet no fully synthetic vaccines have been produced. The production of fully synthetic vaccines has probably not been realized so far due to the structural limitations of linear synthetic peptides to mimic the native shape of protein fragments which is often needed to induce protective antibodies. In this report we used the Bordetella pertussis protein pertactin as a model and show that a novel synthetic scaffold can be used to mimic structurally defined epitopes by confined presentation of several different peptide arms. Guided by modeling a construct was synthesized that induced protective antibodies directed towards a discontinuous epitope. This approach opens up the possibility to the design of new and fully synthetic vaccines that can induce protective antibodies.

9:35 Epitope-Based Multi-Strain Influenza Vaccine – Effective Against H5N1 Avian Flu
Tamar Ben Yedidia, Ph.D., BiondVax Pharmaceuticals Ltd.
A novel approach in vaccine research is the use of epitopes corresponding to immunogenic, conserved sequences of microbial proteins. Influenza virus is characterized by frequent and unpredictable changes of the surface glycoproteins which enable the virus to escape the immune system. Focusing on the development of synthetic recombinant vaccines against this virus, conserved influenza epitopes capable of stimulating B cells, T helper cells and cytotoxic T lymphocytes (CTLs), were individually inserted into the flagellin gene of a Salmonella vaccine strain. The epitopes that elicit the cellular immune response are restricted to the most prevalent HLA alleles in the human population, aiming to confer protection to all. The efficacy of the vaccine was demonstrated in several mice models including standard strains (BALB/c, C57Bl/6), human/mouse chimera in which the engrafted human lymphocytes are functioning and in a transgenic mice model that expresses the human HLA A2.1. The vaccine induces innate immune responses including IFN-gamma secretion and activation of NK cells as well as adoptive immune responses, leading to protective immunity against several strains of influenza. Both intranasal and intramuscular mmunization of transgenic mice with the epitope-based vaccine was effective against lethal infection with H5N1 avian influenza. These results are indicative of the potential of such synthetic constructs as long-range and broad-spectrum vaccines against influenza

10:05 Networking Coffee Break, Poster & Exhibit Viewing Networking

Enhanced Magnitude & Functionality

10:45 Immune Complex Vaccine (ICV) Technology; a Novel Approach in Vaccine Development
Eid Haddad, Ph.D., Senior Research Scientist, R&D, Immunobiosciences, Inc.
A novel approach in vaccine technology has been applied towards the development of viral vaccines which resulted in safer and more immunogenic vaccines. The approach is based on the introduction of the virus in the context of an immune complex (IC) composed of the virus itself in a pre-determined amount bound to a predetermined amount of corresponding neutralizing antibodies. The resulting conjugate is termed the Immune Complex Vaccine (ICV) and is known as the ICV technology. This ICV approach has been successfully applied towards the development and commercialization of two economically important poultry viral vaccines to treat infectious bursal disease and Newcastle disease. Application of the ICV technology to these viruses resulted in the development of safer vaccines that can be administered to chicken embryos in ovo (i.e., in the egg) prior to hatching without effects on performance. Data will be presented supporting safety and efficacy of the ICV technology and demonstrating superiority in vaccine performance over conventional approaches in vaccine development. Additionally, preliminary mechanism of action work has shed some light into a possible working mechanism of the ICV technology. It is believed that when the immune system encounters an antigen as part of a preformed immune complex, quantitative and qualitative changes occur in the immune response to the antigen relative to encountering the antigen alone (Brady, 2005).

11:15 Technology Trends (Sponsorship Available)

11:45 Development of L2 as a Broadly Protective Human Papillomavirus Vaccine
Richard Roden, Ph.D., Associate Professor, Pathology, Johns Hopkins University
Eventual eradication of cervical cancer and cessation of cytologic screening programs requires comprehensive protection against at least 15 oncogenic Human papillomavirus (HPV) genotypes. L1 virus-like particle (VLP)-based vaccines, such as Gardasil and Cervarix, provide largely type-specific protection thereby necessitating highly multivalent formulations to achieve comprehensive protection. A potential alternative is to define a single broadly protective antigen. Vaccination with recombinant L2 capsid protein elicits neutralizing antibody and effectively protects animals from experimental viral challenge. L2 peptide-specific immunity in rabbits is mediated by neutralizing antibody. Importantly, L2 antisera broadly cross-neutralizes multiple divergent HPV types. Indeed we have recently demonstrated that L2 vaccination of rabbits induces protection against highly divergent papillomavirus types. Vaccination with an L2 fusion protein without adjuvant was well tolerated by patients and generated low levels of cross-neutralizing antibodies. However, a potent adjuvant may be required for long lasting L2- specific immunity since the humoral responses of patients to L2 without adjuvant are much weaker than those observed after L1 VLP vaccination. Thus, if the immune responses to L2 can be enhanced with appropriate adjuvants, L2-based vaccines show great promise as an approach to prevent infection by all oncogenic HPV types and related disease.

12:15pm Lunch on Your Own  

Plenary Session - Focus on Adjuvantis

1:40 Chairperson's Remarks

3:15 Networking Refreshment Break, Poster & Exhibit Viewing

4:00 Inducing Anti-Tumor Immunity by Activating Toll-Like Receptor 9
Arthur M. Krieg, M.D., Founder & Chief Scientific Officer, Coley Pharmaceutical Group Inc.
The immune system detects infectious agents using a family of ten Toll-like receptors (TLR), each of which is specific for a type of molecule expressed in pathogens. TLR9 is specific forunmethylated CpG dinucleotides in pathogen DNA, and can be activated with synthetic oligodeoxynucleotides such as PF-3512676. In animal models and in human clinical trials, PF-3512676 activates dendritic cells and induces the generation of tumor-specific CD8+ T cells. PF-3512676 has anti-tumor activity as a monotherapy, or in combination with other approaches, including tumor vaccines, radiotherapy, and chemotherapy, with which it is currently in two phase III clinical trials in NSCLC.

4:30 The New Generation Iscom-Matrix Adjuvant – A Safe and Potent Adjuvant for Demanding Applications
Karin Lövgren Bengtsson, Ph.D., Head R&D, Isconova AB
ISCOMs and the ISCOM technology has been applied in immunological research as well as in experimental and commercial vaccines for about twenty years. The technological developments during these years have been considerable, and the technology that was always regarded as highly efficacious but technically difficult, expensive, and not always satisfactorily safe, has matured into a promising candidate for broad use. Isconova s contribution to technology developments include four animal vaccines on the market, products for laboratory animal applications, large-scale production of purified saponin fractions and Iscom-Matrix, and the new potent LowTox adjuvant with a comfortable safety profile, e.g., for human use.

5:00 A Phase Ib Study of FolateImmune (EC90 with GPI-0100 Adjuvant Followed by EC17) with Low Dose Cytokines Interleukin-2
(IL-2) and Interferon - Alpha; (IFN - alpha) in Patients With Refractory or Metastatic Cancer
Robert J. Amato, D.O., Medical Director, Genitourinary Oncology Program, The Methodist Hospital Research Institute
FolateImmune is a novel therapy that induces an immune response against tumor cells by marking tumor cells with a folate-hapten conjugate targeted to folate-receptor. FolateImmune therapy is comprised of 1) a vaccine containing EC90, 2) an adjuvant (GPI-0100) and 3) a folate-hapten conjugate (Folate-FITC). The folateImmune treatment begins with subcutaneous injections of EC-90 vaccine with GPI-0100 adjuvant to stimulate the production of antibodies to the flourescein hapten. Patients will then receive subcutaneous injections of EC17, an agent intended to form a molecular “bridge” between the tumor cell and the endogenous circulating anti-flourescein immunoglobulin G antibody. This may initiate an Fc-mediated immune response leading to the removal of the antibody-coated tumor cells by a mechanism commonly referred to as an antibody-dependent cellular cytotoxicity and/or phagocytosis.

5:30 PREPS and L-particles- A Novel Herpes Simplex Based Virus Like Particle for Delivery of a Wide Range of Therapeutic Proteins
Ian Pardoe, Ph.D., MB, ChB, MRCGP, Chief Executive and Medical Director, Henderson Morley plc.
As part of the natural infectious cycle, herpes simplex viruses produce virus like particles. These particles contain all of the surface and tegument proteins of the parent virus, but completely lack the nucleocapsid.
These so called L-particles facilitate the natural infection of HSV, so are able to enter cells as if they were viruses. Because of the total lack of DNA, they are unable to replicate. PREPS particles are a modification of L-particles.
Non native proteins that have been engineered into the parent virus, can be delivered functionally intact to cells using PREPS and L-particles. It is possible to engineer the virus to express several antigens simultaneously, so a multivalent cancer vaccine is therefore possible.
L-particles also enhance naked DNA transfection, and its use as an adjuvant for DNA vaccines is being explored.
This talk will briefly highlight the technology and its potential applications.

5:45 End of Day Two