Cambridge Healthtech Institute’s 12th Annual
Vaccine Adjuvants
Improving Vaccine Response through Advanced Technologies
August 31-September 1, 2017 | Sheraton Boston | Boston, MA
Many recently developed vaccines are comprised of recombinant molecules or subunits of pathogenic organisms, requiring formulation with adjuvants to increase and direct the immune response. The benefit of adjuvants is clear: they may reduce the amount of antigen and number of vaccinations needed, accelerate the immune response, increase cross-protection, and improve efficacy in populations that are poor responders. As we continue to confront emerging and re-emerging disease threats and progress toward developing new vaccines to improve global health, there is also an urgent need for the development of effective adjuvants. CHI’s Twelfth Annual Vaccine Adjuvants meeting will cover the latest advances in a range of adjuvants and present a look at future development.
Final Agenda
THURSDAY, August 31
7:45 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
8:30 Modeling of Age-Specific Human Immunity in vitro for Discovery of Small Molecule Adjuvants
Simon Van Haren, Ph.D., Research Fellow, Division of Infectious Diseases, Boston Children's Hospital
Vaccine adjuvants may be most helpful for immunization of high risk populations, such as the very young and the elderly that express distinct immunity. The Precision Vaccines Program at Boston Children’s Hospital is leveraging age-specific human in vitro modeling, high throughput screening and systems biology to develop adjuvanted vaccine formulations tailored to such distinct and vulnerable populations.
9:00 Innate Immune Signaling, STING and Enhancing the Immune Response
Glen N. Barber, Ph.D., Professor & Chair, Cell Biology, University of Miami Miller School of Medicine
Innate immune STING-dependent signaling has been shown to play a key role in facilitating adaptive immune responses. Regulating STING activity exhibits significant promise in strategies designed to augment immune responses against microbial and malignant disease.
9:30 Cellular Effectors of the Humoral Immune Response
Daniel Lingwood, Ph.D., Assistant Professor, Medicine, Harvard Medical School
We describe how dendritic cells, without traditional MHCII-based antigen processing, regulate the initiation of the humoral response to subunit vaccines.
10:00 Coffee Break in the Exhibit Hall (Last Chance for Poster Viewing)
10:45 Vaccine Adjuvants in Cancer and Other Immunotherapy Applications
Nikolai Petrovsky, MBBS, Ph.D., Chairman & Research Director, Vaxine; Professor, Flinders University
This talk will address the benefits of new custom designed vaccine adjuvants for enhancing immunogenicity of vaccines against self-antigens or other poorly immunogenic antigens, including peptides and allergens. This has direct application to development of next-generation vaccines against cancer, allergy, autoimmunity and chronic degenerative diseases such as Alzheimer’s disease.
11:15 Archaeal Lipid Adjuvant Systems for Cancer Vaccine Development
Lakshmi Krishnan, Ph.D., Director & Program Leader, Vaccines and Immunotherapeutics, National Research Council, Canada
A novel class of archaeal lipid adjuvants, currently being developed as a third generation of highly simplified, cost-effective semi-synthetic glycolipid adjuvants that can be formulated with ease for cancer vaccine delivery, will be discussed.
11:45 Development of an Immunotherapeutic Vaccine for Curing Large Solid Tumors in Mice
Joost Oppenheim, M.D., Senior Investigator, Cancer and Inflammation Program, Head, Cellular Immunology Section, National Cancer Institute, National Institutes of Health
We are using a vaccine that aims to activate antitumor responses by synergistically stimulating tumor-infiltrating dendritic cells (DCs) with a combination of high-mobility group nucleosome binding protein 1 (HGMN1), a TLR4 agonist, and R848, a TLR7/8 ligand. We also aim to curtail tumor-associated immunosuppression by co-administering one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose Cytoxan). Treatment of mice with this combination of immunotherapeutics, without giving any antigens, cures a variety of large (1 cm in diameter) tumors and results in long-term specific tumor immunity.
12:15 Cancer Immunotherapy Based on Cross-Priming Liposomes CAF09 – From Animal Model to Clinical Trial
Dennis Christensen, Ph.D., Head of Vaccine Adjuvant Research Group, Center for Vaccine Research, Statens Serum Institute, Denmark
We will here present work that exploits a PRR combination strategy to obtain a liposome formulation that promotes strong CD8+ T-cell responses through efficient cross priming. Our lead candidate CAF09 is a liposomal formulation that exploits two ligands for TH17 responses and optimal cross priming of CD8 responses; a C-type lectin-receptor ligand (monomycolate) and a TLR3 agonist, Poly(I:C). This adjuvant induces very high CD8+ T-cell responses against a range of polypeptide-based vaccines and has strong therapeutic efficacy in different cancer models in mice. The CAF09 formulation is now produced under GMP and will be used in a human clinical immunotherapy trial against prostate cancer in combination with the tumor associated antigen BCL-XI.
12:30 pm Sponsored Presentation (Opportunity Available)
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
2:25 Chairperson’s Remarks
Lakshmi Krishnan, Ph.D., Director & Program Leader, Vaccines and Immunotherapeutics, National Research Council, Canada
2:30 CD40L-Adjuvanted HIV Vaccines
Rama Rao Amara, Ph.D., Professor, Microbiology and Immunology, Emory University
Studies in rhesus macaques show adjuvanting DNA vaccine with CD40L significantly enhances the magnitude and functional quality of vaccine-induced cellular and humoral immunity, and protection against pathogenic simian immunodeficiency virus challenge.
3:00 Driving Humoral Responses against HIV Envelope via Multivalent Display of Env Trimers on Synthetic Liposomes
Talar Tokatlian, Ph.D., Postdoctoral Research Associate, Irvine Lab, Massachusetts Institute of Technology
Multivalent particulate presentation of HIV envelope trimers may contribute to the development of strong and durable humoral responses in immunization against HIV. To this end, we developed strategies to non-covalently and covalently anchor oriented envelope trimer constructs on the surfaces of synthetic liposomes. We have studied their physical properties and stability in vitro, their trafficking in vivo, and immunogenicity in mice and in non-human primates.
3:30 Refreshment Break
4:00 Panel Discussion with the Speakers: Next-Generation Vaccines and Adjuvants
Moderator:
Lakshmi Krishnan, Ph.D., Director & Program Leader, Vaccines and Immunotherapeutics, National Research Council, Canada
Discussion topics include:
- What is the future of personalized, precision vaccines?
- How have recent developments in understanding the immune reponse accelerated vaccine research?
- What new approaches may lead to promising HIV vaccine candidates?
- How will vaccine adjuvants advance the next generation of cancer vaccines?
5:00 End of Day
6:00 Dinner Short Course Registration*
SC4: CRISPR/Cas9 Applications in Immunotherapy
*Separate registration required, please click here for additional information.
FRIDAY, SEPTEMBER 1
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Gokul Swaminathan, Ph.D., Immuno-Biology Group, Merck Cambridge Exploratory Science Center, Merck & Co., Inc.
8:30 Selective RIG-I Agonists as Antivirals and Vaccine Adjuvants
Anna Marie Pyle, Ph.D., William Edward Gilbert Professor, Molecular, Cellular & Developmental Biology, Yale University
RIG-I agonists represent an important class of vaccine adjuvants. The well-developed structural and mechanistic characterization of RIG-I function has led to the design of small, synthetic RNA agonists that are being optimized for potency and bioavailability.
9:00 A Small-Molecule RIG-I Agonist Functions to Enhance Vaccine Protection against Influenza A Virus Infection
Yueh-Ming Loo, Ph.D., Research Assistant Professor, Immunology, University of Washington
We have identified novel, small-molecule RIG-I agonists that bind to and activate RIG-I to induce IRF3 activation and drive innate immune responses to enhance adaptive immunity. These drug-like compounds confer enhanced protection of mice from high dose influenza A virus infection under conditions of suboptimal vaccine dose, showing that RIG-I agonists can serve as adjuvants to potentiate vaccine immunity.
9:30 Investigating Lipid Nanoparticle Formulations in the Context of Infectious Diseases and Immuno-Oncology
Gokul Swaminathan, Ph.D., Immuno-Biology Group, Merck Cambridge Exploratory Science Center, Merck & Co., Inc.
Emerging evidence suggests that bioengineered nanoparticles can be used as immunomodulatory agents. We have previously reported the discovery of novel ionizable cationic lipid nanoparticle (LNPs) based formulations that are safe and efficacious in mice, guinea pigs and non-human primate models of vaccination. In this talk, I will discuss our findings on the mode-of-action of these LNPs and its potential usage in infectious diseases and immune-oncology applications.
10:00 Coffee Break
10:30 A Comparison of TLR3, TLR7/8, and TLR9 Adjuvants Encapsulated in Synthetic Vaccine Particles for Therapeutic Cancer Vaccines
Takashi K. Kishimoto, Ph.D., CSO, Selecta Biosciences
Synthetic vaccine particles encapsulating antigens and various endosomal TLR agonists have been optimized to induce rapid and sustained induction of effector cytolytic T cells. These vaccines demonstrate a significant survival benefit when administered therapeutically in mice with palpable tumors, and also show considerable synergy with checkpoint inhibitors and cytotoxic drugs. We have confirmed the immunogenicity of these vaccines in a pilot study in non-human primates (NHP), comparing TLR3, TLR7/8 and TLR9 agonists for robust induction of antigen-specific T and B cells.
11:00 Feasibility of Freeze Drying of Oil-in-Water Emulsion Adjuvants
Vidyashankara Iyer, Ph.D., Scientist, Formulation Sciences, MedImmune
Oil-in-water emulsions are among the most widely investigated adjuvants. However, most emulsions cannot be readily frozen or lyophilized, due to the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid co-formulation. We will outline the development of a stable, lyophilized squalene emulsion adjuvant. Upon reconstitution, freeze-dried emulsion preparations showed a small increase in particle size and conferred immunogenicity in BALB/c mice similar in potency to freshly-prepared emulsion co-formulations in liquid form.
11:30 Overcoming the Cold-Chain Distribution Hurdle: Development of a Lyophilized Thermostable Single Vial Adjuvanted Vaccine against Tuberculosis
Michelle Chan Archer, Senior Formulations Specialist, Infectious Disease Research Institute
A key limiting factor to widespread vaccine accessibility in developing countries is the lack of reliable product transportation and continuous cold-chain storage. IDRI has developed a lyophilized thermostable tuberculosis vaccine that contains both antigen and adjuvant in a single vial. This prospect has advantages in 1) evading cold-chain dependence, 2) simplifying preparation by avoiding the need for bedside mixing of multiple vials, and 3) extending vaccine shelf lives.
12:00 pm Close of Vaccine Adjuvants