Development of novel vaccine adjuvants capable of activating CD1d-restricted T cells

• Grant number: 16/19077-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2017
• End date: April 30, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Julio Henrique Kravcuks Rozenfeld
• Grantee: Julio Henrique Kravcuks Rozenfeld
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alexandre de Castro Keller ; Karin Do Amaral Riske ; Maria Teresa Moura Lamy

Abstract

Vaccine adjuvants intensify immune responses against co-inoculated antigens and depend on biophysical properties to be efficient. There is great pharmaceutical interest in developing new adjuvants that are able to activate CD1d-restricted T cells, because they recognize lipid antigens and influence immune responses related to several pathogens, autoimmune diseases and cancer. Due to its physical chemical characteristics, the cationic lipid DODAB can serve as an adequate carrier for these lipid antigens. Hence, the aim of this Project is to develop novel vaccine adjuvants that can take advantage of CD1d-restricted T cells by means of characterizing the structure, colloid stability and immunological properties of supramolecular assemblies made of DODAB and different molar fractions of lipids that are agonists of these cells: alpha-galactosylceramide, ganglioside GD3, sulfatide or lysophosphatidylcoline. The biophysical characterization will employ techniques such as Dynamic Light Scattering, Differential Scanning Calorimetry and Electron Paramagnetic Resonance spectroscopy. The biological characterization will employ in vitro and in vivo assays in order to determine the immunogenic potential of the assemblies. This multidisciplinary Project will allow the integration of groups with different expertises and might result in new tools that will harness the CD1d-restricted T cells for use in immunotherapy against cancer, autoimmune diseases and emerging epidemics that depend on effective vaccine strategies (zika, chikungunya and influenza). It will also strenghten Unifesp's Department of Biophysics as an excellence center with the establishment of a new field of research. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARTINS, LETICIA S.; DUARTE, EVANDRO L.; LAMY, M. TERESA; ROZENFELD, JULIO H. K.. Supramolecular organization of a-galactosylceramide in pure dispersions and in cationic DODAB bilayers. Chemistry and Physics of Lipids, v. 232, OCT 2020. (14/50983-3, 16/19077-1, 16/13368-4)

MARTINS, LETICIA S.; NOMURA, DANIELA A.; DUARTE, EVANDRO L.; RISKE, KARIN A.; TERESA LAMY, M.; ROZENFELD, JULIO H. K.. Structural characterization of cationic DODAB bilayers containing C24:1 beta-glucosylceramide. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1861, n. 3, p. 643-650, MAR 1 2019. (16/13368-4, 14/50983-3, 16/19077-1)

DE ANDRADE, LUCAS; DUARTE, EVANDRO L.; LAMY, TERESA; ROZENFELD, JULIO H. K.. Thermotropic Behavior and Structural Organization of C24:1 Sulfatide Dispersions and Its Mixtures with Cationic Bilayers. ACS OMEGA, v. N/A, p. 10-pg., 2023-02-02. (16/19077-1, 16/13368-4, 20/01417-6, 14/50983-3, 21/01593-1)