Research Groups

Molecular Immunology

Research Interests and Description

Group Leader: Oscar Burrone, PhD

Group 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.
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 [Pubmed link]

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 [Pubmed link]

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 [Pubmed link]

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 [Pubmed link]