Keystone Symposia

Sheraton Seattle Hotel Floorplan

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This meeting took place in 2014

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Innovative Vaccine Approaches - RESCHEDULING TO VIRTUAL (Z5)

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The Modes of Action of Vaccine Adjuvants (S1)

Organizer(s) Philippa C. Marrack, Steven Reed and Robert A. Seder
October 8—13, 2014
Sheraton Seattle Hotel • Seattle, WA USA
Discounted Abstract Deadline: Jun 10, 2014
Abstract Deadline: Jul 8, 2014
Scholarship Deadline: Jun 10, 2014
Discounted Registration Deadline: Aug 7, 2014

Sponsored by Pfizer Inc. Part of the Keystone Symposia Global Health Series, supported by the Bill & Melinda Gates Foundation.

Summary of Meeting:
Globally, vaccines are the most effective medical interventions in limiting morbidity and mortality against infections. Effective vaccines are administered in a variety of formulations and include not only portions of their target but also adjuvants. Adjuvants can improve the magnitude and breadth of the immune response and immunological memory against the target and also determine the nature of the generated immune response. Almost all vaccines that are now in use include adjuvants, such as nucleic acids from the target organisms, in the case of attenuated virus vaccines, insoluble aluminum salts (alum), oil-in-water emulsions (MF-59) or formulated toll-like receptor ligands (MPL-TLR4). However, the world still lacks consistently effective vaccines against many infectious agents, tuberculosis, malaria and HIV and against cancers. Therefore much current research is devoted to identification of newer adjuvants, adjuvants that will safely induce the type of immune response that will most effectively deal with its target. In many cases the precise mode of action of the adjuvant is not known. For example the mode of action of alum, an adjuvant that has been used in vaccines since the 1930s and generates excellent antibody responses, is still inadequately understood. This conference will focus on the cell and molecular mechanisms of action of old and new adjuvants and other immunomodulatory agents and their use in various vaccines against infectious diseases and cancer.

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Conference Program    Print  |   View meeting in 12 hr (am/pm) time


Keystone Symposia: Arrival and Registration

Seattle Sheraton Metropolitan Ballroom Foyer
Coffee Break

Westin Hotel Ballroom Foyer
Grand Challenges & Keystone Symposia Joint Scientific Session: Innovation Panel Plenary

* Sue Desmond-Hellman, CEO of the Bill & Melinda Gates Foundation

- Francis Collins, Director, National Institutes of Health
- Bill Gates, Co-Chair of the Bill & Melinda Gates Foundation

- Arunachalam Muruganantham, Founder of Jayaashree Industries

- Amy Smith, Founder and Co-Director, D-Lab, Massachusetts Institute of Technology

Seattle Westin
Grand Challenges & Keystone Symposia: Joint Reception

Seattle Westin



Metropolitan Ballroom
Cell Death and Nucleic Acids as Adjuvants
To understand how nucleic acids and other components of the host act as immunological adjuvants.

Metropolitan Ballroom
* Emilio Flano, Seres Therapeutics, USA

Michael Gale, Jr., University of Washington, USA
Targeting RIG-I for Vaccine Adjuvant Activity

Ken J. Ishii, National Institute of Biomedical Innovation, Health and Nutrition, Japan
Nucleic Acids as "Built-in" or "Inducible" Adjuvant during Vaccination

Anna Marie Pyle, Yale University, USA
Small RIG-I Ligands and their Development as Antivirals and Vaccine Adjuvants

Thomas W. Dubensky, Jr., Tempest Therapeutics, USA
Development of Human STING-Activating Synthetic Cyclic Dinucleotide Derivatives as Adjuvants for Cancer Immunotherapy and Infectious Disease

Robert E. Johnston, Global Vaccines, Inc., USA
Short Talk: Biological Adjuvant Activity of Alphavirus Replicon Particles

Coffee Break

Metropolitan Ballroom Foyer
Poster Setup

Metropolitan Ballroom
Poster Viewing

Metropolitan Ballroom
On Own for Lunch

Workshop 1: TLRs and STING

Metropolitan Ballroom A
* Robert R. Kane, Baylor University, USA
Synthesis and Protein Conjugation of TLR Agonists

Aideen C. Allen, Institut de Pharmacologie et de Biologie Structurale, France
A Novel TLR2 Agonist from B. pertussis Is a more Effective Adjuvant than Alum for an Acellular Pertussis Vaccine

Roger H. Brookes, Sanofi Pasteur, Canada
Dose-Ranging Analysis of H4 TB Vaccine Formulations in Mouse and Fresh Human Whole Blood Reveal that an Excess of IC31® Adjuvant Is Needed for Immunomodulation

Mark T. Orr, Infectious Disease Research Institute, USA
Mechanistic Insights Into the TH1 Induction Capacity of Formulated TLR4 Agonist Adjuvants

Caroline Junqueira, Centro de Pesquisas René Rachou/ Fiocruz, Brazil
Attenuated Trypanosoma cruzi Expressing Tumor Antigen to Induce a Potent Antitumor Immunity Mediated by TLRs Agonists

Andres Sanchez Alberti, Universidad de Buenos Aires - CONICET, Argentina
Sting Agonist and Antigen Design as a Vaccine Model to Combat Parasitic Chronic Infections

* Yueh-Ming Loo, AstraZeneca, USA
Small Molecule RIG-I Agonists as Vaccine Adjuvants

Shan Lu, University of Massachusetts Medical Center, USA
Involvement of Aim2 Inflammasome Pathway in Antigen Specific Antibody Responses Elicited by HA-Expressing Influenza DNA Vaccine

Workshop 2: T Cells

Metropolitan Ballroom B
* Nancy A. Hosken, University of Washington, USA

Alicja Misiak, Trinity College Dublin, Ireland
Lung gammadelta T Cells Mount Innate and Adaptive Immune Responses to Bordetella pertussis – Implications for Pertussis Vaccines

Chiung-Yu Hung, University of Texas at San Antonio, USA
Th17 Immunity is Essential for Optimal Protection Against Coccidioides Infection

* Stephen M. Carpenter, Regeneron Pharmaceuticals, USA
Heavily-Armed but Outnumbered: A Selective Loss of Memory CD8+ T Cells during Tuberculosis may Eclipse the Benefit of Vaccination

Dipendra Kumar Mitra, All India Institute of Medical Sciences - AIIMS, India
Programed Death Receptor-1 Preferentially Inhibits Poly-Functional T Cells in Human Tuberculosis

Yasser A. Aldhamen, Michigan State University, USA
Therapeutic Blockade of CRACC, a Novel Immune Modulation Strategy for Enhancing Memory T Cell Immune Responses

Robert Weinkove, Capital & Coast District Health Board, New Zealand
Glycolipid-Peptide Conjugates Exploit Natural Killer T Cells to Enhance Peptide-Specific CD8+ T Cell Responses

Coffee Available

Metropolitan Ballroom Foyer
The Action of Adjuvants on Dendritic Cell Subsets
To learn about the use of adjuvants, alone, or in combination with biologicals, in cancer vaccines.

Metropolitan Ballroom
* Jonathan A. Deane, Kumquat Biosciences, USA

Ofer Levy, Boston Children's Hospital, USA
In vitro Modeling to Inform Age-Specific Adjuvanted Vaccine Development

Claudia Jakubzick, Dartmouth College, USA
Short Talk: Dendritic Cell Subsets Require cis-Activation for Cytotoxic CD8 T Cell Induction

Karin Loré, Karolinska Institutet, Sweden
Innate Immune Activation in vivo after Adjuvant Administration

Social Hour with Lite Bites

Metropolitan Ballroom
Poster Session 1

Metropolitan Ballroom



Metropolitan Ballroom
Immunostimulatory Properties of Particles
Particles have long been known to have immunostimulatory properties. This session will discuss the mechanisms by which particles have this effect.

Metropolitan Ballroom
* Rima L. McLeod, University of Illinois, USA

Tarek M. Fahmy, Yale University, USA
Modular Nanomaterials Orchestrating the Direction and Magnitude of the Immune Response

Gary J. Nabel, Sanofi, USA
Synthetic Nanoparticle and Virus-Like Particle Vaccines for Influenza and Alphaviruses: Developing New Technologies to Address Growing Public Health Concerns

James I. Andorko, University of Maryland, USA
Short Talk: Intrinsic Immunogenicity of Rapidly Degradable Polycations: Role of Physicochemical Properties

Marcela Rincon-Restrepo, École Polytechnique Fédérale de Lausanne, Switzerland
Short Talk: Polymersomes Enhance the Induction of Follicular Helper CD4 T Cells and Promote Long Antibody Responses

Darrell J. Irvine, Massachusetts Institute of Technology, USA
Controlling Immunization Potency and Safety through Molecular Targeting of Vaccines to Lymph Nodes

Steven Reed, Infectious Disease Research Institute, USA
Status and Clinical Development of Next Generation of TLR 4 Based Adjuvants

Coffee Break

Metropolitan Ballroom Foyer
Poster Setup

Metropolitan Ballroom
Poster Viewing

Metropolitan Ballroom
On Own for Lunch

Workshop on Adjuvant Formulation
Session to cover three case studies on adjuvant formulation. Co-sponsored by the Global HIV Vaccine Enterprise, the Bill &Melinda Gates Foundation and the Division of AIDS, National Institute of Allergy Infectious Diseases, National Institutes of Health.

Metropolitan Ballroom A
Coffee Available

Metropolitan Ballroom Foyer
Lipids, Emulsions and Detergents
To understand the ways in which these unexpected materials improve immune responses.

Metropolitan Ballroom
* Christopher B. Fox, Infectious Disease Research Institute, USA

Yan Shi, University of Calgary, Canada
Redirecting MHC Class II Antigen for MHC Class I Crosspresentation during Phagocytosis

Anja Seubert, GlaxoSmithKline, Italy
The Mechanism of Action of the Oil-in-Water Adjuvant MF59

Eugene Maraskovsky, CSL Limited, Australia
Mechanism of Action for Induction of Innate and Adaptive Immune Responses using ISCOMATRIX® Adjuvant

Anthony L. Desbien, Aduro Biotech, USA
Short Talk: A Role for the Inflammasome during Immunization with the TLR4 Agonist GLA when Combined with a Squalene Emulsion

Social Hour with Lite Bites

Metropolitan Ballroom
Poster Session 2

Metropolitan Ballroom



Metropolitan Ballroom
Human Genetics and Adjuvants
The genetic make up of individuals affects their reponses to vaccines. This issue will be discussed here.

Metropolitan Ballroom
* Angelika Riemer, German Cancer Research Center /DKFZ, Germany

Jean-Laurent Casanova, Rockefeller University, USA
Toward a Genetic Theory of Childhood Infectious Diseases

Rafick Sekaly, Emory University, USA
Predictors of Adjuvant and Vaccine Efficacy

Emmanuel Mignot, Stanford University School of Medicine, USA
Narcolepsy, Vaccination and Immunogenetics

Robert L. Coffman, Dynavax Technologies, USA
Systems Biology Analysis of the Human Response to Hepatitis B Vaccines using Alum or CpG Oligonucleotide Adjuvants

Taiki Aoshi, National Institute of Biomedical Innovation, Japan
Short Talk: Adjuvant Database Project: Comprehensive Transcriptome Analysis in Animal Models

Coffee Break

Metropolitan Ballroom Foyer
Poster Setup

Metropolitan Ballroom
Poster Viewing

Metropolitan Ballroom
On Own for Lunch

Workshop 3: VLPs and Antigen Presentation

Metropolitan Ballroom A
* Darrell J. Irvine, Massachusetts Institute of Technology, USA

Rajesh Kumar, Tulane University, USA
Plasmodium falciparum Pfs25 Produced in E. coli Delivered with Various Nanoparticles Exhibit Strong Malaria Transmission Blocking Immunity

Masayuki Hayashi, Mitsubishi Tanabe Pharma, Japan
AdvaxTM, a Formulation of Delta Inulin Microparticles, Is a Non-Canonical Adjuvant that Induces Distinct Immune Response Depending on the Property of Vaccine Antigen

Karen Martins, USAMRIID, USA
Impact of Adjuvants on VLP-Mediated Protection from Ebola Virus Challenge

Marie-Ève Lebel, INRS, Institut Armand Frappier Research Centre, Canada
Plant Virus-Like Nanoparticles as Adjuvant: Mechanisms of Action and Application for Cancer Immunotherapy

Gokul Swaminathan, Merck Research Laboratories Cambridge Exploratory Science Center, USA
A Novel Cationic Lipid Nanoparticle Adjuvant Significantly Enhances B Cell and T Cell Responses to Recombinant Sub-Unit Viral Vaccines

Gervais Rioux, Université Laval, Canada
Effect of PapMV Adjuvant on the Immune Response Kinetic of Inactivated Flu Vaccine

* Elizabeth A. Leadbetter, University of Texas Long School of Medicine, USA
Glycolipid Adjuvant-Containing Nanoparticles Protect Against Streptococcus Pneumoniae

Workshop 4: Adjuvant Profiling

Metropolitan Ballroom B
* Mario Barro, Sanofi Pasteur, USA
Adjuvants for Novel and More Efficacious Influenza Vaccines

Christopher B. Fox, Infectious Disease Research Institute, USA
Benefits and Limitations of in vitro Human Whole Blood and Macrophage Cell Line Assays to Evaluate Activity of Adjuvant Formulations

Wivine Burny, GlaxoSmithKline, Belgium
Associations between Reactogenicity Symptoms and Parameters of the Early Immune Response to Adjuvanted Vaccines in Humans

Takuo Mizukami, National Institute of Infectious Diseases, Japan
System Vaccinology Enables to Evaluate the Safety of the Influenza Vaccine and the Adjuvant with a Multiplex Gene Detection System of Novel Biomarkers in the Pre-Clinical Study and Lot Release Test

Jourdan K. Posner, University of Hawaii, Manoa, USA
The Effect of Possible Vaccine Adjuvants on the Differentiation and Activation of B Cell Subsets Important to the Germinal Center Reaction

Katy M. Graef, BIO Ventures for Global Health, USA
Accelerating Vaccine Development through Cross-Sector Collaborations

Emily Field, Loyola University Chicago, USA
Developing Adenovirus-Vector Vaccines for MRSA

Coffee Available

Metropolitan Ballroom Foyer
Guiding the Immune Response
Different adjuvants generate different types of immune response. The means by which they do this will be discussed here.

Metropolitan Ballroom
* Martha A. Alexander-Miller, Wake Forest University School of Medicine, USA

Kingston H.G. Mills, Trinity Biomedical Sciences Institute (TBSI), Ireland
TLR-Based Adjuvants for Infectious Disease and Cancer Vaccines - Enhancing Effector Over Regulatory T Cell Responses

Ross M. Kedl, University of Colorado Denver, USA
T Cell Vaccinology: Lessons Learned in Primates

Philippa C. Marrack, HHMI/National Jewish Health, USA
Host DNA Acts as an Adjuvant in Unexpected Situations

Michael Y. Gerner, NIAID, National Institutes of Health, USA
Short Talk: Strategically Localized Lymph-Sampling Dendritic Cells Promote Rapid T Cell Responses to Particulate Vaccines and Lymph-Borne Pathogens

Social Hour with Lite Bites

Metropolitan Ballroom
Poster Session 3

Metropolitan Ballroom



Metropolitan Ballroom
Adjuvants for Still Unmet Needs
Here we will discuss the use of old and new adjuvants in new vaccines.

Metropolitan Ballroom
* Susan Baldwin, Infectious Disease Research Institute, USA

Bali Pulendran, Stanford University School of Medicine, USA
Systems Vaccinology: Enabling Rational Vaccine Design with Systems Biology

Lawrence Corey, Fred Hutchinson Cancer Research Center, USA
Concepts in the Immunotherapy of HSV 2 Infections Role of Adjuvants

Nathalie Garçon, Bioaster, France
Adjuvants for Vaccines against the Big 3: An Historical Perspective

Peter L. Andersen, Statens Serum Institut, Denmark
Tailoring Adjuvants for Tuberculosis Vaccines

Derek T. O'Hagan, GlaxoSmithKline Vaccines, USA
Can We Design a Single Delivery System for a Broad Range of Molecules from Small Molecule Adjuvants, to Proteins and RNA Vaccines?

Nitasha R. Bennett, University of Wisconsin, Madison, USA
Short Talk: Triggering B and T Cell Activation with Synthetic Multivalent Antigens

Michael Fichter, University Medical Center Mainz, Germany
Short Talk: Yeast-Based Expression and Purification of Recombinant Hepatitis C Virus Proteins for the Development of Novel Polymeric Protein Nanovaccines

Coffee Break

Metropolitan Ballroom Foyer
On Own for Lunch

Workshop 5: Vaccine Mechanisms and Formulations

Metropolitan Ballroom A
* Christopher Jewell, University of Maryland, USA

Hongming Hu, Providence Cancer Center, USA
TLR and NALP3 Inflammasome Dependent Innate Immune Responses to Tumor-Derived Autohagosomes (DRibbles)

Daniel Villarreal, Advaxis, USA
Immunoadjuvant IL-33 Amplifies Memory CD8 T Cells and Enhances Antigen-Specific Tumor and Viral Immunity

* Arnaud Didierlaurent, University of Geneva, Switzerland
Early NK Cell Activation as a Result of MPL and QS-21 Combination Controls the Adjuvant effect Induced by the Human Adjuvant System AS01

Iain David Welsby, Université Libre de Bruxelles, Belgium
Understanding the Cellular and Molecular Mechanisms Involved in the Adjuvanticity of a Liposomal QS-21 Formulation

Charlotte Givord, Université Libre de Bruxelles, Belgium
Deciphering the Signaling Pathways Involved in the Immunostimulatory Properties of the Adjuvant System AS03

Amy Galliher-Beckley, MFB Fertility, USA
Novel Low-Cost, Easy-to-Use Emulsion Is a Stable Adjuvant and Induces Long-Lasting Antibody Responses to Swine Influenza Virus and Mycoplasma hyopneumoniae

Workshop 6: Role of Dendritic Cells in vivo and Dendritic Cell Targeting

Metropolitan Ballroom B
* Ross M. Kedl, University of Colorado Denver, USA

* Richard A. Kroczek, Robert Koch-Institute, Germany
Targeting of Antigen into XCR1+ Dendritic Cells Combined with a Non-Viral Boost Regime Induces Massive CD8+ T Cell Cytotoxicity Capable of Controlling 50xLD50 Listeria Infection and Eradicating Established Tumors

Monica Montes, Baylor Institute for Immunology Research, USA
Anti-Human CD40 Antibodies with Selective Functional Properties

Rossella Cioncada, University of Siena, Italy
Vaccine Adjuvant MF59 Promotes in vivo Differentiation of Monocyte-Derived Dendritic Cells within Medullary Compartment of the Draining Lymph Nodes, which Correlates with Increased Ability to Trigger T Cell Response

Stefaan De Koker, University of Gent, Belgium
Inflammatory DCs Constitute a Crucial Source of IL-12 but Fail to Present Antigen in Case of CpG-Adjuvanted Vaccines

Laura E. Noges, Fred Hutchinson Cancer Research Center, USA
Host DNA Plays a Role in Generating CD4 T Cell Responses to Various Vaccine Adjuvants

Elizabeth A. Thompson, Karolinska Institute, Sweden
Intravenous Administration of an Agonistic CD40 Antibody Induces Strong T Cell Responses in the Lung

Chinnaswamy Jagannath, Houston Methodist Research Institute, USA
Induction of Autophagy as an Emerging Molecular Mechanism of Immunoadjvants

Frédéric Martinon, INSERM U1184 Commissariat Energie Atomique (CEA) - Université Paris-Saclay, France
TLR Ligands Indirectly Activate Skin Langerhans Cells by Triggering Local Recruitment of Inflammatory Cells

Workshop 7: Vaccine Delivery

Tarek Hamouda, NanoBio Corp., USA
Intranasal Nanoemulsion-Adjuvanted Genital Herpes Vaccine; A New Approach Utilizing Mucosal Immunity to Induce Protection Against HSV2 Infections

* Olivia M. Flynn, University College Cork, Ireland
Immunogenicity of dmLT Adjuvanted Vaccines in ImmuPatch Dissolvable Microneedle Patches in Mice

Chintan Hareshbhai Kapadia, University of North Carolina at Chapel Hill, USA
PRINT Nanoparticulate Subunit Vaccine to Combat Cancer

Sudhir Pai Kasturi, Emory University, USA
Programming the Magnitude and Persistence of Humoral Immunity Against HIV Using Novel TLR Ligands Delivered in Biodegradable Nanoparticles

Kouji Kobiyama, National Institute of Biomedical Innovation, Japan
K3-SPG, a Nano-Particulate TLR9 Agonistic Ligand Works as a Potent IFN Inducer and CTL Adjuvant

* Aaron Palmer Esser-Kahn, University of California, Irvine, USA
Controlling Adjuvant Activity with Light

Coffee Available

Metropolitan Ballroom Foyer
New Approaches to Vaccines

Metropolitan Ballroom
* Laura Shackelton, Bill & Melinda Gates Foundation, USA

Jenny P.Y. Ting, University of North Carolina at Chapel Hill, USA
Impact of NLR Proteins on Innate and Adaptive Immunity

Robert A. Seder, NIAID, National Institutes of Health, USA
Adjuvants for HIV Vaccines, Mice versus Humans

Meeting Wrap-Up: Outcomes and Future Directions (Organizers)

Metropolitan Ballroom
Social Hour with Lite Bites

Metropolitan Ballroom

Metropolitan Ballroom



*Session Chair †Invited, not yet responded.

Keystone Symposia thanks our Sponsors(s) for generously supporting this meeting:

Bill & Melinda Gates Foundation Pfizer Inc.

We gratefully acknowledge the generous grant for this conference provided by:

National Institutes of Health

Grant No. 1R13AI114173-01

The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

We gratefully acknowledge additional in-kind support for this conference from those foregoing speaker expense reimbursements:

CSL Limited

Dynavax Technologies Corporation

Novartis Vaccines and Diagnostics

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