INCT of Investigation in Immunology

Abstract

The Institute for Investigation in Immunology, iii, initially a Millenium Institute created in 2001, studies infectious diseases, HIV/AIDS, allergy, autoimmune diseases, transplantation and primary immunodeficiency. These diseases have strong immunological components, and are health problems that affect millions in our country and throughout the world. Besides the social and economic relevance, these diseases are also important biological models, the study of which allows the increase of knowledge on their pathophysiology aiming at therapeutic interventions based on pathogenesis. Immunology was the first branch of Molecular Medicine to develop and to use biodrugs. Today, approximately 50 monoclonal antibody and recombinant proteins are in commercial use, but the acquisition of novel products depends on understanding the causes and mechanisms involved in the pathologic processes behind these diseases, which is still lagging, and therefore so is treatment. An integrated approach that includes clinical, molecular, epidemiologic tools, bioinformatics and systems biology will be required to find solutions for these issues. Broader approaches are needed for the innovative vaccine design and novel immunotherapies for graft rejection, infectious diseases and their sequels, autoimmune processes, and allergies. The iii is focused in developing translational research aiming to test, in humans, the novel strategies developed experimentally. In the previous stages, we recruited and trained the human resources and put in place the facilities and equipment to develop the technological routes needed to dissect the pathogenic mechanisms allowing the design of biological therapeutics to target such mechanisms and test them in animal models, to create a portfolio of new products. During its third phase (2008-2014), besides upgrading our portfolio of immunobiologicals by adding patents and grants for clinical trials, the iii graduated 42 MSc and 82 PhD students, and 21 post-doctoral fellows, and generated 468 scientific publications. In autoimmunity, we will now advance the development of our candidate vaccine to prevent S. pyogenes infection and Rheumatic Fever with the initial phase I and II clinical trials, besides trying out novel immunomodulatory (natural or recombinant probiotics) to treat Crohn’s disease. The intervention with such probiotics will also be tested in animal models, kidney transplant patients and in infectious diseases like leishmaniasis and HIV/AlDS. Several studies are planned to study HIV pathogenesis and the development of AIDS, and also to study adjuvant therapy. After ending preclinical trials in primates, we will be able to conduct a phase I clinical trial of the first candidate AIDS vaccine developed in Brazil by researchers from iii, and already patented. Studies on the cellular and molecular immunology of primary immunodeficiency will further our knowledge about its pathogenesis. We will test previously identified novel strategies for treatment of visceral and tegumentary leishmaniasis. An important screening of neutralizing antibodies against dengue fever to help understand pathogenesis and treatment of this disease will be carried out. Human monoclonal antibodies neutralizing Tetanus toxin will be generated for therapy. In the area of transplantation, we will study the mechanisms involved in graft rejection and we will also test two immunobiologicals developed by iii to improve immunoregulation in the setting of transplantation. In the area of allergy, we will study newly identified Brazilian allergens, food allergy, the search for novel mutations associated with allergic diseases, and the interference of A. lumbricoides parasites in asthma. In addition to translational research, we have developed a network to share expertise among the groups that are part of the Institute to train students, personnel, and researchers. To further increase our networking potential we developed platforms that allow us to work in a matrix of different themes. The current proposal counts 6 platforms: Proteomics, Epidemiology and Clinical Trials, Immunobiologicals, Bioinformatics, Quality Assessment and Assurance, and Teaching and Interaction with Society. These platforms interact with all the iii research areas. We created also three research axes: Immunoregulation, Microbiomes, and Systems Biology to enhance collaborative research between the different research groups. Finally, seeking to overcome the already known bottlenecks, we have included highly qualified staff to conduct preclinical toxicology tests in models established in different species, in addition to physicians with expertise in clinical trials, especially concerning phase I and trials, where local expertise is still scant. In its current form, the iii is built by a unique combination of individuals capable of taking products it has already developed from the bench to the bedside, as well as acquiring new knowledge, products and guidelines for public health policies according to its mission of raising Brazilian Immunology to international standards. (AU)