21st Century Health Challenges
Prevention of the rapid spread of infectious diseases is a key scientific challenge for our global community. Easily accessible global travel, deforestation, people living in close proximity to animals that have lost their natural habitats and climate change all contribute to the high risk of pandemics. Global pandemics and pathogens spreading into new geographical locations are no longer exclusive to the realm of science fiction. We have witnessed Avian Influenza, SARS and H1N1 rapidly spread across the globe while mosquito-borne, tropical diseases such as Dengue Fever are occurring for the first time in the United States. New vaccine approaches are required to meet newly emerging global needs and iCubed is well positioned to rapidly respond to the health challenges of the 21st century.
The Institute for Immunology and Informatics (iCubed) was established in 2008 under the leadership of Annie De Groot as part of the University of Rhode Island’s (URI) emerging biotechnology program. The institute maintains offices and laboratory space in the historic Shepard Building as part of URI’s Feinstein Providence Campus. Both of iCubed’s Chief Scientists, Dr’s. Anne De Groot and Alan Rothman, are recognized as leaders in their field, not only for their research expertise, but also for their ability to foster collaboration and mentor the next generation of scientists.
Anne De Groot, M.D. is recognized for her “genome–to–vaccine” methodologies. Her team at iCubed applies cutting-edge bioinformatic tools to accelerate the development of treatments and cures for a number of diseases such as HIV, Influenza and Burkholderia. The Institute aims to quickly make these tools available to the global research community. VaccineNation names Dr. De Groot as one of the most influential people contributing to the vaccine industry.
Alan Rothman, M.D. has recently garnered over $20M in NIH funding and has notably established URI’s first Center of Biomedical Research Excellence (COBRE). Additionally, Dr. Rothman serves as the Director for the Dengue Hemorrhagic Fever Project, a longstanding research collaboration involving studies of dengue virus transmission, infection, and illness with an overall goal of advancing the treatment and prevention of disease.
iCubed’s Research Focus
iCubed’s research focuses on creating new and safer vaccines. We also explore new methods of predicting and treating adverse immune responses. iCubed supports a wide variety of training efforts that provide opportunities to advance women and students in science which include unique technology toolkits and hands-on laboratory experiences.
We envision a world free of diseases caused by infection.
To improve human and animal health by applying the power of genomics and informatics to the design of better vaccines, diagnostics, and therapeutics.
We also seek to inspire and advance the role of women in science.
A world free of diseases caused by infection.
Developing new vaccines and immunotherapeutics, generating new knowledge by engaging in basic and applied research, and training the next generation of scientists.
New Biological Entities
Biotechnology is a rapidly expanding field leading to the development of new medicines, agricultural products, and immuno-therapeutics such as monoclonal antibodies and vaccines. New Biological Entities (NBEs) comprising therapeutic proteins, vaccines and antibodies, provided biotech companies with revenues of greater than $70 billion in 2007 (Ernst and Young). NBE approvals nearly doubled in the United States in the last decade (Center for Study of Drug Development/Tufts University 2011). While some universities have been slow to respond to the demand for qualified graduates, the University of Rhode Island (URI) has embraced this opportunity and has been rapidly expanding the number of biotech-related educational offerings over the past few years.
With the addition of the Institute of Immunology and Informatics (iCubed) in 2008, URI has become a recognized leader in the field of vaccine discovery. iCubed investigators and collaborators (through the $13 million TRIAD U19 grant from the National Institutes of Health) are fully invested in transferring their knowledge and experience in these complex issues surrounding vaccine discovery to the next generation of scientists. Training is one of the core missions of the iCubed, as is development of safer, more effective, genome-derived vaccines.
iCubed Focus: Faster, Safer and Fewer Vaccines for the 21st Century
Excitement about vaccines is palpable. While they are certainly the greatest safeguard of human health, saving literally millions of lives per year, new ideas about using vaccines to treat cancer and autoimmune disease are generating significant interest in academia and industry. Research on new vaccines is leading to the introduction of novel materials such as naked DNA, crab-shell derived chitosan vaccine delivery vehicles, and insect-cell produced antigens to name just a few. The fact that there are no effective vaccines for emerging infectious diseases lends even greater urgency to vaccine research. Faster, safer vaccine development is a critical area of US research focus, according to the Health and Human Services Secretary Kathleen Sebelius, who said that the US must build a “21st century medical countermeasure enterprise that is modern, flexible, and equipped to respond quickly and effectively to any threats that arise”. The need for this nation-wide effort to improve vaccine design and production was illustrated by industry-wide delays in the development of a vaccine for the pandemic strain of H1N1 swine flu. The iCubed is currently funded through the $13 million TRIAD CCHI (U19 Center grant) and is actively contributing to national efforts to speed the design and development of vaccines, including selection of safer and more efficient delivery methods that are critically important to advance vaccines in the next century.
A Unique Approach
The iCubed excels in immunoinformatics-driven vaccine development, colloquially known as “gene-to-vaccine”. The approach involves computer-driven analysis of genome sequences, selection of immunogenic segments, and composition of vaccines in silico. The next step in the process is to validate the vaccine candidates in vitro and in vivo, using methods developed in the iCubed laboratories. A wide array of vaccine delivery technologies are under evaluation, including monoclonal antibodies (Moise), liposomes (Bothun, De Groot), and DNA vaccines (De Groot with the Department of Defense). Using immunoinformatics tools, research also is being conducted on eliminating parts of vaccines that may contribute to deleterious immune responses (Rothman). Collaborations extend internationally to Thailand (Dengue virus, Rothman), and Mali (HIV, TB, HPV, De Groot). Research collaborations have been developed with Steve Williams (filaria, Smith College), another investigator who is involved in the iCubed program. Each of these cross-cutting areas of research, comprising experience that covers the biotech field ‘from gene to vaccine’ is currently being integrated into the activities of the iCubed.
Industry Leaders lending their skills to iCubed Translational program
Dr. De Groot has made it her mission to train the next generation of researchers to design safer, more efficacious, and more accessible vaccines. She actively coordinates training opportunities with Greg Paquette, Director of the Biotechnology and Manufacturing program and Edward Bozzi, Associate Professor Clinical, under the College of the Environment and Life Sciences (CELS). Currently, undergraduate and master’s-level URI students are exposed to iCubed research and have access to biotechnology courses and hands-on laboratory experiences through the biotechnology program at CELS. At the iCubed, students are able to engage in Ph.D.-level research and training in vaccine and biologics development lead by iCubed researchers.
iCubed has access to tools for “genes-to-vaccines” development that were originally developed by Dr. De Groot at EpiVax, Inc. (a iCubed industry partner). These tools are being successfully applied to the design of vaccines for Tularemia, Burkholderia (biodefense agents), HIV, TB, HCV, Tick-borne-disease, and H. pylori by iCubed researchers. Additional collaborations at the iCubed are designing new vaccines for the equine encephalitis viruses WEE/EEE/VEE (biodefense agents, in collaboration with EpiVax and the Department of Defense) and young researchers were trained to apply the tools to Neglected Tropical Diseases (NTD’s) over the past year. The tools allow rapid scanning of bacterial and viral genomes for highly immunogenic components and the rapid concatenation of these components in a delivery vehicle (such as a plasmid or pseudoprotein). The prototype vaccines are validated in vitro (in HLA binding and T cell assays) and in vivo (in HLA transgenic mice). Areas of active research also include elimination of epitopes that are cross-conserved with the human microbiome. Collectively, iCubed’s approaches are gaining industrial acceptance when selecting the best lead candidates to carry forward from preclinical to clinical development, and are reducing the risk of failure in the clinical setting.
iCubed Economic Impact
Rhode Island is actively developing its knowledge economy with a concerted effort by local businesses, universities, hospitals and government officials, and Dr. De Groot has been a driver in this effort. For example, Dr. De Groot holds a highly successful course for entrepreneurship. This cross-institutional collaboration teaches scientists and business-trained individuals the principles of biotechnology start-up with a focus on companies that support vaccine research. This course has been repeatedly profiled as a success story in Providence by the business community and both academic and industry leaders participate in teaching the course. The focus of this course is to create jobs in Rhode Island. Clearly, staring businesses and hiring employees has a direct economic impact on the state.
Projects that have garnered Federal Interest
The Department of Defense (DOD) and the NIH are highly interested in vaccine-related research, and are actively funding projects in vaccines for infectious diseases, biodefense, neglected tropical diseases, and vaccine delivery vehicles. These federal institutions are engaged in funding projects that bring new therapeutics to the patient, so called translational research. The iCubed currently is funded through NIH grants that focus both on education as well as research in translational vaccine design for emerging infectious diseases and biodefense agents.
Translational Research: Infectious Disease Immunology
There is an ongoing need for research to advance the fight against infectious diseases, both in the U.S. and globally. Infectious diseases that have been known for centuries, including measles, influenza, and malaria, continue to cause substantial numbers of illnesses and deaths. In addition, new or re-emerging infectious disease threats are being recognized on a regular basis, such as dengue, HIV/AIDS, and Ebola. Many of these diseases are particularly a problem for less-developed, low-resource countries, and are considered “neglected” diseases.
There is a great deal of interest in manipulating the human immune system to address the growing number and diversity of pathogens, through vaccines and other drugs. It is critical to achieve a better understanding of how the human immune response interacts with different microorganisms in the natural setting. iCubed is actively contributing to this effort. In collaboration with physicians and scientists in the US and internationally, we are studying people exposed to dengue and HIV to learn about the mechanisms of infection and disease.