The Wyss’ infection vaccine technology was assembled organically, as was the entrepreneurial team that strives to bring it to the world
By Benjamin Boettner and Jessica Leff
The COVID-19 crisis has made one thing clear: emerging infectious diseases are a real threat that must be confronted using entirely new approaches. The Wyss Institute has developed OMNIVAX, an extremely broad-spectrum infection vaccine technology that can help tackle infectious diseases caused by virtually any type of pathogen. OMNIVAX is rooted in the successful biomaterials-based cancer vaccine that was created by a team led by Wyss Institute Core Faculty member David Mooney, Ph.D., which has been licensed to Novartis for cancer applications. The OMNIVAX infection vaccine is highly modular in that it can be rapidly manufactured using pathogen-specific antigens, a common set of immune-stimulating adjuvants, cytokines, and self-assembling biomaterials. In contrast to most other vaccine approaches, OMNIVAX vaccines only need to be administered in a single injection to provide prolonged stimulation of the immune system and potentiate pathogen specific immunity, which represents a major advantage for large-scale vaccination programs.
The concept of this new type of infection vaccine came to life organically by developers of the cancer vaccine technology liaising with other Wyss researchers who were working intensely to develop ways to capture and eliminating pathogens in septic patients. Edward Doherty, a Lead Senior Staff Scientist working with Mooney in the Wyss’ Immuno-Materials platform, and Mike Super, Ph.D., who plays a similar role in the Institute’s Bioinspired Therapeutics & Diagnostics platform led by Wyss Founding Director Donald Ingber, M.D., Ph.D., started to fervently discuss the simple question, “could we design a type of vaccine that generates immune responses as strong as those observed with the cancer vaccine but targeted to infectious diseases simply by including antigens from key pathogens instead of tumor cells in the biomaterial scaffold backbone of the vaccine?” This conversation between Doherty and Super quickly gained momentum, marking the beginning of a Wyss project that produced the first infection vaccine prototype within months.
A multi-disciplinary team which has made it its mission to translate this promising vaccine technology into a potential commercial product for clinical use, is currently focusing on three main infectious disease areas: COVID-19 caused by SARS-CoV-2, influenza caused by a virus that constantly escapes from existing vaccines; and urinary tract infections triggered by pathogenic E. coli strains that often become recurrent or resistant to antibiotics.
Meet the lead
Edward Doherty, a member of the Wyss’ Advanced Technology Team and lead of the infection vaccine project, joined the Wyss Institute after having spent 25 years in the biotech industry, where he worked on drug delivery, artificial organs, surgical sealants, and new types of biomaterials for different uses in medicine. Through his preceding studies at Northeastern University in Boston, which earned him a bachelor’s degree in biology and chemistry and a master’s degree in regulatory affairs, and various experiences in biotech, he honed a diverse skill set that spans the gamut of chemical engineering, management, process development, project management, and regulatory affairs. While pushing technologies towards their intended markets, Doherty had to be cheek by jowl with academic partners to tightly align translational developments with the latest results from basic research.
“When I walked through the door into the Wyss Institute about 10 years ago, I was entrusted with bringing the biomaterials-based cancer vaccine technology from Dave Mooney’s group to a clinical trial at the Dana-Farber Cancer Institute, where it eventually was successfully investigated in patients with melanoma,” said Doherty. “This was immensely exciting, and gave our idea of developing a similar approach as an infection vaccine platform critical impetus. After our initial conversations with Mike Super and the Wyss pathogen capture and sepsis group in 2017, and a few well-designed studies, we quickly knew that we had something unique and powerful: a potent immune-recruiting and activating biomaterial that as a pathogen-loaded vaccine would need to be injected only once, and thus could provide a real breakthrough in the broader vaccine arena.”
Doherty, who actually performed early rabbit immunization experiments himself, has since shifted his main focus to tackle the managerial challenges in the infection vaccine platform, which entail project management, budgeting, the continuously increasing business development and outreach efforts, and, importantly, “herding the cats and maintaining focus.” He has been working closely with Wyss Business Development Lead Jessica McDonough, Ph.D., who has been instrumental in raising awareness of the project in the investment community and honing Doherty’s business acumen. Doherty is taking on his many challenges with a special sense of humor, which is engrained in his DNA, and for which, in an earlier life, he found a temporary outlet in the disguise of a joke and costumes shop that he kept with his brother-in-law in Waltham, Massachusetts.
Self-assembly: from vaccine to team
Before Mark Cartwright obtained a Ph.D. at Boston University, his career had taken a few unusual turns. Following his undergraduate studies in neurobiology at McGill University in Montreal, Canada, he became a carpenter and renovated homes, some of which were historic buildings. Cartwright then attended North Bennet Street School in Boston, America’s oldest trade school before returning to his first love: science. Joining a neurobiology group at Boston University Medical School as a research technician, he immersed himself in the study of neurodegenerative diseases and the pathogenic causes of Lyme disease, which ultimately led him to his Ph.D. in pharmacology and experimental therapeutics at Boston University. After conducting postdoctoral work related to aging and metabolic disorders, he took a job at EMD Serono developing Phage Display approaches for the discovery of novel antibodies as candidates for cancer therapies. “Working at EMD Serono gave me really good exposure to the whole industrial side of science,” said Cartwright. “You had strict milestones and the research was high-throughput and targeted.” This experience also made him a valuable asset for the Wyss Institute, which recruited him in 2010 to join the group of George Church, Ph.D., about a month after Doherty had commenced his work at the Wyss. “I thought, ‘this is a cool opportunity.’ The Wyss was much smaller back then, but it had already started its journey towards an exciting future that I wanted to be part of.”
Shortly thereafter, Cartwright was offered another opportunity to pivot in a new direction. Ingber and Super were looking to build a high-profile microbiology group that turned out to be instrumental for their development of different pathogen capture approaches for therapeutic and diagnostic purposes. As the project grew, Cartwright became the leader of this DARPA-funded microbiology team who had a growing collection of pathogenic strains and the expertise to grow and analyze them. “At that point, I knew Ed Doherty and Mike Super had been talking about crossing our technology with the cancer vaccine for some time. Finally, we decided to give it a shot. Once we had optimized the first prototypes, we vaccinated mice with them, and got really good results on the first pass. Suddenly, people became very interested,” Cartwright recalled.
Now, Cartwright is the technical lead on the project. He still uses his background in microbiology and molecular biology to work on the pathogen side of the OMNIVAX technology. At the same time, he helps keep the project focused on its key target indications: UTIs, influenza, and COVID-19. He is instrumental in making connections across the Boston scientific community, including the Wyss’ liaison with Boston University’s BSL-4 lab that fulfills the highest safety standards for virus research, and steering the project forward.
Microbiology on turbo
Benjamin Seiler, after finishing his undergraduate degree in microbiology at the University of New Hampshire in 2010, first followed a calling to Harvard Medical School, where he joined Assistant Director and microbiologist Robin Ross, Ph.D. as part of the New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (NERCE). The group’s biomolecule production core, which Seiler co-managed, was involved in the development of preventive and therapeutic interventions against Priority Pathogens listed by the National Institute of Allergy and Infectious Diseases (NIAID) as emerging and re-emerging infectious disease threats. Seiler interacted with multiple investigators in the lab’s sphere, with most of his work focused on large scale fermentation and downstream purification of microbial proteins to better understand their roles in the pathogenesis of various infectious diseases.
After a few years, he felt the urge to expand his personal skill set and horizons further and connected with Ingber’s and Super’s pathogen capture team at the Wyss Institute, which at the time had set out to build a BL2 microbe-oriented lab to broaden the scope of their pathogen capture program. “The team was screening clinically relevant pathogens as potential targets for capture using an engineered protein, which was right in my wheelhouse,” said Seiler, who joined Super and Cartwright in the project. The DARPA-funded program spawned more and more applications, and, “with a lot of infectious disease initiatives happening, the idea of the biomaterials-based infection vaccine had begun and necessitated some substantial microbiology work.” Eventually, Seiler fully dedicated himself to the infection vaccine project.
Along the way, Seiler expanded his expertise into the development of functional assays for evaluating the vaccines. “We had to optimize animal models and understand the pathogenic burden in different organ systems first so that we could then determine if our vaccine was efficacious.” Seiler is working side by side at the bench with Fernanda Langellotto, Ph.D., the team’s lead of the in vivo and in vitro assay development, and hand in hand with entire team. “We think our novel vaccine approach brings a superior strategy to combating difficult to treat infectious diseases,” said Seiler, who besides confronting the coronavirus pandemic in the lab, also found a way to deal with it at home with a full-fledged indoor gardening initiative.
The final piece
The team was completed when Fernanda (Nada) Langellotto joined the Wyss in 2018. Hailing from Italy, Langellotto started her scientific career by obtaining a master’s degree in veterinary medicine at the University of Naples Federico II, focusing on the science and technology of animal production. She then moved to Boston to pursue a Ph.D. in cellular and molecular biology as a visiting student at Massachusetts General Hospital. After postdoctoral work in ophthalmology and gene therapy at UMass Medical School and, subsequently, being a research fellow at Boston Children’s Hospital and Boston University where she studied lung and breast cancer respectively, she decided to get a taste of the rich biotech industry around her, and worked for different companies applying her training to cancer immunotherapy. According to Langellotto, “among the highlights of my time in industry were the excitement of seeing drug compounds become FDA-approved and commercialized, and learning the value of a strong team culture.”
The OMNIVAX Institute Project caught her attention as soon as she joined the Wyss Institute, because it would allow her to apply her skills and knowledge in immunology to a new and fascinating challenge. After her initial validation experiments, she quickly came to believe in the vaccine technology’s potential. “I put a lot of effort into making this technology move forward, only based on the strong hunch that it could be very powerful. Our work so far has really convinced me that this technology can truly be what we are hoping it to be,” Langellotto explained.
Langellotto quickly found a crucial role to play on the team: designing in vivo studies to understand the immunology behind vaccines and validating them using a range of in vitro methods. For her, it remains a priority to follow experiments from beginning to end in order to best comprehend the results. Also, her extensive experience with in vivo pharmacology and continuous interaction with Wyss staff veterinarian Amanda Graveline, D.V.M., gives her a solid understanding of the animal models used in the team’s in vivo experiments, which range from small (such as mice to hamsters) to large (such as rabbits, pigs, and cows) and in the future hopefully non-human primates. At the same time, she enjoys learning from the experience of assisting on the business development and managerial sides of the project and embraces her multifaceted role in quickly filling in the OMNIVAX jigsaw with Doherty fully acknowledging that “she has actually been a huge driving force of this project.”
Working as a matrix in a matrix
Under Mooney’s continuous scientific mentorship starting in 2017, OMNIVAX graduated from a platform project at the Wyss’ Immuno-materials platform to a Validation Project and then to an Institute Project. The project received additional Technology and Business Development support with each new step up in the Wyss’ unique Technology Translation funnel, thereby reducing risk on the path to commercialization. “The concept for the project was entirely born in the spirit of the Wyss’ natural self-assembly capabilities that inspire many of its projects. It started by two groups organically coming together, and once we saw the initial results, we just kept running with it until we had built the confidence that we needed to believe that the infection vaccine technology could be a game changer in the vaccine world,” said Ed Doherty.
Over the course of the project’s relatively short life, multiple additional Wyss researchers, including Research Assistants Des White, Chyenne Yeager, Shanda Lightbrown, and Christopher Johnson; Senior Staff Scientist Mohan Karkada, Ph.D.; Senior Staff Scientist Alexander Stafford, and others participated in working through critical challenges and refining key aspects of the technology.
Now, in the present highly complementary and interdisciplinary team their unique experiences and skills synergize to optimize the vaccine technology for the specific disease applications. “We constantly bounce a lot of ideas off each other for each of these goals, and thus can gather different perspectives that help us solve challenges as they arise,” Seiler explained, and Langellotto added: “The culture of the team is a crucial piece of the puzzle, and we’re very lucky there. I truly believe that working as a matrix is the most important thing to make this project eventually work for the many people around the globe who really need it.”