Cambridge Healthtech Institute’s Inaugural
DNA- and RNA-Based Vaccines Symposium
Part of the Eleventh Annual ImVacS: Immunization and Vaccine Summit
December 6, 2016 | Revere Hotel | Boston, MA

Nucleic acid vaccines, often called “third generation” vaccines, have many advantages, especially in the effort to increase response time to emerging infectious diseases. Less expensive to produce, they are also more scalable and have the potential to greatly simplify vaccination logistics. Cambridge Healthtech Institute’s Inaugural DNA- and RNA-Based Vaccines Symposium will cover the recent advances in DNA and RNA vaccine technologies that promise to improve efficacy and safety for this appealing platform.

Final Agenda

Tuesday, December 6

8:00 am Symposium Registration and Morning Coffee

Improving Efficacy and Maximizing Immunogenicity of DNA Vaccines

8:25 Chairperson’s Remarks

William Watt, Ph.D., President & CEO, EpiThany, Inc.; University of Washington Tumor Vaccine Group

8:30 DNA Vaccination at the Crossroads of Acquired andInnate Immunities

Shixia Wang, D.V.M., Ph.D., Professor, Medicine, University of Massachusetts Medical School

The use of DNA immunization to elicit high quality antibody responses is receiving more attention. DNA prime-protein boost is highly effective in eliciting cross-subtype binding and functional antibodies in both animal and human studies. New data demonstrate that DNA immunization can take advantage of recently identified intracellular mechanisms involved in both acquired and innate immune response pathways.

9:00 Improving the Potency of DNA-Based Cancer Vaccines Using SynCon® Technology

Jian Yan, Ph.D., Associate Director, Antigen Discovery and Design, Inovio Pharmaceuticals

Inovio synthetic consensus (SynCon®) technology is a multi-phase DNA vaccine design strategy. Breaking tolerance remains a challenge for cancer vaccine development. Instead of using germline sequences, we incorporated SynCon® design strategy into our cancer vaccine design. Our data showed that SynCon® antigens exhibited stronger ability to break tolerance and induced robust cellular immune responses in both murine and non-human primate models. In a tumor challenge model, we demonstrated that the SynCon® antigen was able to slow tumor growth compared to animals vaccinated with the germline cancer antigen.

9:30 Adjuvant Strategies for Maximizing Immunogenicity of Protein, Polysaccharide and DNA Vaccines

Nikolai Petrovsky, MBBS, Ph.D., Chairman & Research Director, Vaxine; Professor, Flinders University

Highly adaptable pathogens including influenza, tuberculosis and HIV continue to circumvent attempts to control them using traditional vaccine approaches. Hence new advances and technologies are needed to overcome such challenges. In addition to novel computational approaches to intelligent antigen design, novel approaches including polysaccharide, lipid, DNA-encoded and RNA-encoded antigens, and alternative intranasal, intrapulmonary and transdermal vaccine delivery approaches, are all designed to induce stronger immunity at the right geographical locations. Whilst adjuvants have proved indispensable for enhancing the immunogenicity of traditional intramuscularly delivered protein vaccines, far less is known about optimal adjuvant strategies for use with these novel vaccine technologies. This talk will discuss how adjuvanting strategies can be tailored to a broad range of different antigen types and vaccine delivery approaches.

10:00 Coffee Break

Case Studies of DNA Vaccines

10:30 DNA-Launched Live Attenuated Vaccines

Peter Pushko, Ph.D., President & CSO, Medigen, Inc.

A novel DNA vaccine platform (iDNA®) uses plasmid DNA to launch live-attenuated RNA virus vaccines in vivo. After administration, the DNA synthesizes the full-length viral genomic RNA and initiates limited replication of live-attenuated virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. With this technology, the field of DNA vaccines is expanded to include a novel type of DNA vaccine that launches live-attenuated viruses.

11:00 A DNA Vaccine to Prevent Congenital Cytomegalovirus Infections

Michael McVoy, Ph.D., Professor, Pediatrics, Virginia Commonwealth University

Development of a congenital cytomegalovirus vaccine is a public health priority. DNA vaccines expressing cytomegalovirus glycoprotein B (gB) or pentameric complex subunits UL128, UL130, or UL131A were evaluated in mice and rabbits. The gB vaccine induced complement-dependent fibroblast and epithelial entry neutralizing responses that were comparable to those induced by natural infection. Thus, a gB-expressing DNA may be an important component of a vaccine for prevention of congenital cytomegalovirus infections.

11:30 Th1 Epitope Selection Unlocks the Potential of Plasmid DNA Vaccines for Cancer

William Watt, Ph.D., President & CEO, EpiThany, Inc.; University of Washington Tumor Vaccine Group

Cancer vaccines have travelled an arduous route towards efficacy, and the most promising approaches entering clinical development years ago continue to fall short in later studies. Many approaches have not improved the vaccine antigen component substantially, focusing instead on vector and administration. The EpiThany vaccine platform mines Th1-selective epitopes from tumor antigens, unlocking the true potential of the plasmid DNA vector to show consistent anti-tumor immunogenicity in the clinic.

12:00 pm Retinaldehyde Dehydrogenase 2 as a Molecular Adjuvant for Enhancement of Mucosal Immunity during DNA Vaccination

Kenneth Bagley, Ph.D., Head, Adjuvant Discovery & Development, Profectus BioSciences

12:30 Enjoy Lunch on Your Own

RNA-Based Vaccines

1:55 Chairperson’s Remarks

Jeffrey Ulmer, Ph.D., Head, Preclinical R&D US, GSK Vaccines

2:00 Self-Amplifying mRNA Vaccines

Jeffrey Ulmer, Ph.D., Head, Preclinical R&D US, GSK Vaccines

Recent advancements have demonstrated that vaccines based on self-amplifying mRNA have the potential to combine the positive attributes of other types of vaccines without their limitations. Although the mRNA vaccine field is in its infancy, the prospects are promising. The broad utility and rapid response potential of this novel vaccine technology may enable a new generation of vaccines able to address the health challenges of the 21st century.

2:30 RNA-Encoded Synthetic Gene Circuits for Tissue-Specific Expression and Small Molecule-Based Dosage Control of Therapeutic Proteins

Ron Weiss, Ph.D., Professor, Biological Engineering, MIT

RNA therapeutics are an attractive alternative to traditional DNA-based therapies, providing transient expression with minimal risk of genomic integration. However, the majority of current applications, ranging from vaccination to genetic reprogramming, rely solely upon constitutive expression. We have employed synthetic biology to expand the potential of RNA expression platforms to include cell-type specific expression and small molecule mediated dose control of therapeutic proteins. Synthetic biology aims to create and characterize libraries of highly predictable and modular genetic parts that can be combined to produce genetic circuits. To this end, we establish a collection of RNA-based parts that can modulate translation. We demonstrate that RNA-based circuits can be regulated using either exogenous siRNAs or endogenous miRNAs. Finally, we couple our genetic parts with small molecule responsive elements to form an RNA-only circuit platform that can dynamically control expression of multiple therapeutic proteins using external inputs.

3:00 Characterizing mRNA-Based Vaccines: From Single Molecules to the Whole Body

Philip Santangelo, Ph.D., Associate Professor, Biomedical Engineering, Georgia Tech

mRNA-based vaccines present enormous opportunities but also many challenges. In my talk, I’ll discuss cutting edge techniques for characterizing mRNA delivery, mRNA trafficking and innate immune responses from the single cell level to the level of the whole organism, using visible and near-IR fluorescence and techniques as well as PET/CT.

3:30 Evaluating Lipid Nanoparticles for mRNA Vaccine Delivery

Matthias Oberli, Ph.D., Research Associate, Langer Lab, David H. Koch Institute for Integrative Cancer Research, MIT

4:00 Close of Symposium

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