Research Groups
Molecular Immunology
Research Interests and Description
Group Leader: Oscar Burrone, PhDGroup Members
Research Interests
DNA vaccines, antibody engineering, anti-idiotypic Abs, dendritic cells, membrane-IgE, Wiskott-Aldrich syndrome, molecular biology of rotavirus.Description of Research
DNA vaccines
The Group studies strategies for the use of DNA vaccines
mainly against tumours. Previous work in a B-cell lymphoma model allowed us to
define protocols with significant protective effect combining design of the
immunogen and antigen delivery, including prime boost via gene gun and
recombinant AAV. In collaboration with the University of Pisa we have recently
commenced a Clinical Trial to test our vaccine in patients with B-cell
lymphoma. We are investigating the efficacy of specific targeting of tumour
associated antigens to Dendritic cells for activation of cytotoxic T cells and
induction of antibody responses in a murine HER2 solid tumour model. Different DCs targeting molecules have
been constructed and tested as DNA vaccines for anti-HER2 antibodies and T-cell
responses via cross-presentation.
We have extended our experience on DNA vaccines to the
design of immunogens against the envelope protein of Dengue virus, a high
impact human pathogen (with ICGEB, New Dehli (link to Khanna) and to VP4 and
VP7 of rotaivurs (with the University of Zürich). We are now testing constructs
designed to induce rotavirus–VP4 specific and Dengue non-crossreactive
serotype-specific, neutralising antibodies.
Igs and antibody engineering
Interest focuses on the use of antibody derived domains for
biotechnological applications, such as the development methods for specific
targeting of proteins in vivo for their degradation via appropriately
engineered V region domains. We also investigate methods to achieve long term
expression of recombinant antibodies for sustained passive immunisation against
tumours. Our interest is to define
efficacy of constructs derived from alternative C-region isotypes. We
investigate the role of the Extracellular Membrane Proximal Domain (EMPD) of
human membrane IgE, with the aim of understanding its structure and the control
of apoptosis in mature IgE+ B cells and the identification of membrane
partners.
Dendritic cells
A major interest is the role of DCs in the pathogenesis of
the Wiskott-Aldrich syndrome, a primary immunodeficiency characterized by
recurrent infections and autoimmune phenomena. Recent results suggest that
exaggerated DCs activation upon bacterial infection may contribute to
dysregulated T cell activation. To translate our basic findings into
application we are following reconstitution of DCs functions upon gene
correction in a preclinical model of gene therapy (with the TIGET Institute,
Milan). In parallel we investigate aspects of DC biology to understand their
antigen presenting functions and aim to characterize the mechanisms that
regulate remodeling of the cytoskeleton, polarity proteins and vesicular
trafficking during formation of immune synapse with T cells.
Molecular Biology of Rotavirus
Rotavirus are dsRNA viruses with a cytoplasmic replication
cycle. Genome viral replication and the initial steps of virus morphogenesis
take place within viroplasms where several viral proteins are recruited. The
mechanisms and requirements for the different viral components to localise and
assemble into viroplasms remain obscure. We have been able to define conditions
for the assembly of VLS (viroplasm like structures) able to recruit the
relevant components; an important step to investigate virus morphogenesis.
Efforts are underway to identify cellular partners of viroplasms and assembly
of recombinant infective particles.
Recent Publications
Arnoldi, F., Burrone, O.R. 2009. Role of viral non-structural proteins in rotavirus replication. Future Virology 4, 185-197
López-Requena, A., Burrone, OR. 2009. Anti-Idiotypic Antibodies and “Tumor-Only” Antigens: An Update. Open Immun. J. 2, 1-8
Cesco-Gaspere, M., Zentilin, L., Giacca, M., Burrone, O.R. 2008.
Boosting anti-idiotype immune response with recombinant AAV enhances
tumour protection induced by Gene Gun vaccination. Sc. J. Imm. 68, 58-66
Predonzani,
A., Arnoldi, F., López-Requena, A., Burrone, O.R. 2008. In vivo
site-specific biotinylation of proteins within the secretory pathway
using a single vector system. BMC Biotechnology 8, 41
Pulecio
J., Tagliani, E., Scholer, A., Prete F., Fetler, L., Burrone, O.R.,
Benvenuti, F. 2008. Expression of Wiskott-Aldrich syndrome protein in
dendritic cells regulates synapse formation and activation of naive
CD8+ T cells. J.Immunol, 181, 1135-1142
Tagliani E., Guermonprez
P., Sepúlveda J., Lopez Bravo M., Ardavin C., Amigorena S., Benvenuti,
F., Burrone O.R. 2008. Selection of an antibody library identifies a
pathway to induce immunity by targeting CD36 on steady state CD8a+
dendritic cells. J. Immunol. 180, 3201-3209
