Established in 2008, the Institute for Immunology and Informatics has quickly developed a devoted following in the research community. To accommodate that interest, iCubed holds two annual meetings to discuss the latest developments, research and theories in the world of immunology and vaccines. Each October brings the Vaccine Renaissance Conference, also known as Vax Ren. In the spring, the Immunogenicity – Determinants and Correlates Conference, or IDC. Both meetings offer extensive presentations from a wide range of speakers tailored to the given audience. For more information on each conference, please visit the links below.
Internship Opportunities at iCubed
iCubed internship programs welcome eligible college, graduate, and professional students to intern with iCubed investigators.
Working at iCubed gives opportunities:
- To gain knowledge and be mentored by scientists who will help guide you in your research.
- Develop your technical skills and bench experience by participating in an existing research investigation.
- Network with mentors and peers within the biomedical community
- Participate in a wide range of activities, including lecture series during the summer featuring iCubed senior staff, journal club, and peer networking opportunities.
For more information about:
- Summer internship opportunities, click here.
- URI biotech program internship opportunities, click here.
These programs give you an opportunity to:
- Gain knowledge and be mentored by iCubed researchers who will help guide you in learning and performing techniques used in a modern day biotech research facility. Researchers include Principal Investigators, Post Doctoral Fellows, Research Associates and Graduate Students.
- Gain hands-on research experience that relates directly to today’s major global health concerns.
GVRD (Global Vaccine, Research and Development)
The GVRD lab is the main research lab for iCubed, and houses a number of varied research projects. Currently in progress:
- HP, a vaccine project targeting h. pylori
- Multipath, a vaccine project targeting b. mallei, b. pseudomallei and f. tularensis.
- FishVAX, a vaccine project targeting v. anguillarum, an aquatic pathogen affecting fish used in aquaculture
- DEC205, a technology project which aims to develop a detolerized targeting antibody
- Thyroiditis Project, focused on combating autoimmune disorders
- Lysostaphin, a deimmunization project of a biological therapeutic
LVIP (Laboratory for Viral Immunity and Pathogenesis)
- Flavivirus Infections: Pathogenesis and Prevention, investigating mechanisms involved in pathogenesis of dengue hemorrhagic fever / dengue shock syndrome
- Heterologous Immunity, a project focusing on immune responses during secondary dengue viral infections
CMI Core (Cell Mediated Immunity) – support lab for all iCubed laboratory research including the following:
- Flow Cytometry, Cytometric Bead Array
- iCubed’s main BSLII cell and tissue culture facility
- ELISpot (Enzyme Linked Immunosorbent Spot) preparation and analysis
- Preparation of liposome delivery vehicles for vaccines and other biologics
- Cryopreservation and storage
- HLA binding assays and other ELISA based assays
- Animal Facility
Current Research Projects
Biodefense vaccines against Category B bioterror agents Burkholderia pseudomallei (BPM) and Burkholderia mallei (BM) are needed, as they are both easily accessible to terrorists and have strong weaponization potential. Burkholderia cepaciae (BC), a related pathogen, causes chronic lung infections in cystic fibrosis patients. Since BPM, BM and BC are intracellular bacteria, they are excellent targets for T cell-based vaccines. However, the sheer volume of available genomic data requires the aid of immunoinformatics for vaccine design. Recent results show it is possible to rapidly identify promiscuous T helper epitopes conserved across multiple Burkholderia species and test their binding to HLA in vitro. The next step in our process will be to test the epitopes ex vivo using peripheral leukocytes from BC, BPM infected humans and for immunogenicity in human HLA transgenic mice.
The Immunome project
Tools available to map T cell epitopes in whole virus and bacterial vaccines are of interest because of the potential for cross-protection against like pathogens, or, alternatively, deleterious cross-reactive immune responses to autologous proteins or the human microbiome. Our ability to differentiate between adaptive immune responses elicited by vaccines that are both protective and also pathogen-specific and responses to host or host-associated sequences is critical to foster the development of better vaccines in the future. Thus the laboratories of De Groot and Moise (TRIAD CCHI at URI) collaborating with Rothman (URI) and Selin (UMass) and Sztein are collaborating to explore the role of cross-reactive T cell responses in vaccination. Thus we propose to (i) measure the modulation of immune responses to common vaccines due to pre-existing T cell responses to common viral pathogens (Epstein Barr and influenza) and (ii) delineate cross-reactive T cell responses between a bacterial vaccine (S. Typhi) and the human microbiome. Exploration of the intersecting T-cell epitope and TCR specificities between vaccines, self, commensals, and common human pathogens is critically important to building better vaccines for human use. Likewise, better understanding of vaccine-induced immune responses that could jeopardize self-tolerance and/or human microbiome homeostasis is critical to effective vaccine design.
Some years ago, researchers at EpiVax developed a tool to map and predict T cell epitopes in pigs. Similarly to EpiMatrix, this tool was based on the pocket profile method. The team developed both class I and class II prediction tools. One matrix was developed for the allele SLA-DRB1*D, which is the only class II allele expressed by NIH research mini-pigs.The matrices are currently in re-development and the current goals is to newer data that is now available data (SLA sequences, pig T cell epitopes) to improve this approach and develop matrices for more SLA alleles of outbred populations of pigs.The current project involves Andres Gutierrez Nunes, an undergraduate student in Dr. De Groot’s laboratory, Frances Terry and Bill Martin of EpiVax, Crystal Loving of USDA< and Paolo Verardi from the University of Connecticut. In addition to Pig prediction tools, Fish tools are being developed and tested in collaboration with Marta Gomez Chiarri at URI CELS.
Neglected Tropical Diseases
Approximately 1 billion people – one sixth of the world’s population – suffer from one or more neglected tropical diseases. The World Health Organization has defined Neglected Tropical Diseases as diseases that affect a majority of the developing world but have been underfunded in terms of research and product development dollars (http://www.who.int/neglected_diseases/diseases/en/). They include (among others): Buruli ulcer, Chagas disease, Cholera, Dengue, Dracunculensis, Leishmaniasis, Onchocerciasis, Schistosomiasis, and Trachoma. Genomes for many of these pathogens are becoming available due to research efforts worldwide, and so the iCubed is collaborating with researchers from all over the world to identify new epitopes and design vaccines using the CCHI funded ‘iVAX’ toolkit. The iCubed runs several training session per year -following these training sessions, NTD researchers can gain access to a dedicated website containing their genomes of choice for their own epitope-mapping use.
Improved Vaccine Delivery by Removal of Tolerogenic Signals in Dendritic Cell Targeting Antibodies
The goal of this project is to improve antibody-based platforms for vaccine antigen delivery to dendritic cells by elimination of regulatory T cell activation signals naturally found in antibodies. Regulatory T-cell epitopes derived from conserved regions of human immunoglobulins are presented in the context of MHC to ‘natural’ Tregs that go on to suppress immune response in human PBMCs in vitro. The corresponding murine epitopes have been shown to suppress in vivo immune response in HLA DR4 transgenic mice. We are designing and testing epitope-modified dendritic cell targeting antibodies, initially in a mouse model in vitro and in vivo and then ex vivo using human blood leukocytes. We hypothesize that removing tolerogenic signals in dendritic cell targeting antibodies carrying vaccine antigens will convert an otherwise immunosuppressive milieu into one that helps bring about pro-inflammatory
responses to promote effective vaccination.
An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design
The goal of this research program is to characterize the human immunological response to Helicobacter pylori T-cell epitopes. H. pylori immunopathogenesis has been thoroughly characterized, providing important insights into how this bacterial pathogen interfaces with the host immune system and evades host defenses, allowing it to persist in a hostile gastric environment. How it manages to trigger epitope-specific immune responses at the molecular level is not yet well understood and requires further investigation in order to develop
prophylactic and therapeutic vaccines. The advent of sequenced H. pylori genomes and immuno-informatics tools capable of mining them enables experimental analysis of sequences that directly stimulate and inhibit multi-functional human T cell responses. Moreover, the availability of these data makes it possible to molecularly characterize the impact of H. pylori on autologous and heterologous immunity. We are working to (1) identify immunogenic epitopes in humanized mouse models that are transgenic for human leukocyte antigens (HLA), (2) examine the antigenicity of potential vaccine candidate T-cell epitopes in human peripheral blood and stomach tissue and (3) characterize immune responses elicited by epitopes with sequences homologous between humans and microorganisms that infect and colonize humans.
Induction of Antigen-Specific Tolerance in Autoimmune Thyroiditis
Autoimmune diseases require therapies that restore regulation of an immune system that has gone awry. A logical strategy to accomplish this in the case of Graves’ Disease is to employ naturally occurring regulatory T cells (Tregs) to create the immunological milieu needed to activate functionally weakened Tregs that are Graves’-specific. We have identified a set of natural, human regulatory T-cell epitopes (Tregitopes) in immunoglobulins that are recognized by T cells exhibiting the phenotypic characteristics of natural Treg cells. These Tregitopes have been shown to specifically activate CD4+ T cells leading to up-regulation of Treg markers CD25/FoxP3, as well as increased expression of pro-regulatory cytokines and chemokines. Importantly, Tregitope co-incubation leads to suppression of antigen-specific allergic Th2 response. We are investigating the capacity for Tregitopes to reduce Th2 responses in PBMC from Graves’ subjects and induce TSHR-specific adaptive Tregs, which would be the basis for a therapy that will reduce Th2-dependent autoantibody levels.
My laboratory is studying the role of virus-specific T lymphocytes in the clinical manifestations of dengue viral disease. In one study, we are analyzing the kinetics of viral replication, T cell and monocyte activation, and cytokine production in children with acute dengue virus infections. In another study, we are defining immunologic responses prior to dengue infection that are associated with an increased risk for severe disease.
For more information, please contact:
Carey Medin, Ph.D.
iCubed Internship Program Coordinator
80 Washington Street
Providence, R.I. 02903