October 9, 1951 |
|Fields||Immunology and cell biology|
|Institutions||Institute for Research in Biomedicine in Bellinzona
Professor, D-BIOL, ETH-Zurich
|Alma mater||University of Pavia|
|Known for||Antigen processing and presentation, dendritic cell biology, lymphocyte activation and traffic and immunological memory human immunology and discoveries involving innate and adaptive immunity.|
Antonio Lanzavecchia (born in Varese October 9, 1951) is an Italian immunologist. He was a fellow of Collegio Borromeo and obtained his degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases.
Since 1980 he focussed on human immunology, first at the University of Genoa, at the Basel Institute for Immunology and, from 1999 at the Institute for Research in Biomedicine in Bellinzona, of which he is the founding Director. He has been teaching Immunology at the University of Genoa and the University of Siena and since 2009 is professor of Human Immunology at the Swiss Federal Institute of Technology Zurich. Since January 2014 he had been appointed President of the Fondazione Regionale per la Ricerca Biomedica of the Region Lombardy, Italy.
His research has covered several aspects of human immunology. Antigen processing and presentation. Using clones of antigen-specific B and T cells, he demonstrated that B cells efficiently capture, via membrane immunoglobulins, the specific antigen, which is then internalized, and processed into peptides, which are presented to T helper cells in an extraordinarily efficient manner (1). This study uncovered a critical step in the process of T-B cell cooperation that is essential for high affinity antibody production and represents the basis for the development of glycoconjugate vaccines. In subsequent studies, he showed that antigens can be effectively targeted to surface molecules other than membrane immunoglobulins (2, 3), a finding that has contributed to current strategies of antigen targeting to improve vaccination. Finally, he addressed the role of HLA class II molecules as receptors for self versus foreign peptides and showed how inflammatory stimuli can enhance the loading of pathogen-derived peptides on newly synthesized HLA Class II molecules so as to favour host-protective immunity (4, 7).
Monocyte-derived dendritic cells: In the early Nineties the analysis of dendritic cells was impeded because of their low number and the inability to generate them at will for detailed study of their function. In collaboration with his colleague Federica Sallusto, Lanzavecchia helped solve this fundamental problem when he discovered that human monocytes could be induced to differentiate in vitro into “immature” dendritic cells that resemble those that function as sentinels in peripheral tissues (8), contributing to the rapid advancement of the field in the late nineties and paving the way for the use of antigen-loaded dendritic cells as vaccines. Using these dendritic cells he studied in detail the cell biology of the maturation process and identified the microbial and endogenous stimuli that trigger dendritic cell maturation (7, 10).
Immunological memory: While the property of memory in the adaptive system had been known for decades, it was Lanzavecchia’s laboratory that described in humans a fundamental division of memory T cells into two major subtypes, central memory and effector memory T cells, which play distinct roles in secondary immune responses (11). He proposed that central memory T cells, which migrate to secondary lymphoid organs, represent memory stem cells responsible for recall responses and the long-term maintenance of the memory pool. In contrast, effector memory T cells that home to peripheral tissues provide immediate protection but have shorter lifespan and reconstitution capacity. Based on original studies on the roles of T cell receptor triggering, sustained signalling and costimulation in T cell activation (12-14), Lanzavecchia also proposed a progressive model of T cell differentiation to explain the generation of central and effector memory T cells within a single clone of antigen-primed T cells (15). The discovery of central memory and effector memory cells has been particularly relevant in the context of T cell-based vaccines that aim at inducing durable and protective immunity.
Human monoclonal antibodies and vaccine design: Taking advantage of his studies on human memory B cells (16), Lanazvecchia developed novel and robust methods to immortalize human memory B cells and to preserve single plasma cells in culture (17, 18). He used these methods to interrogate the memory repertoire of selected individuals to isolate monoclonal antibodies with unique specificities. Several examples illustrate the power and utility of this approach. Neutralizing antibodies were isolated against SARS, cytomegalovirus, avian influenza and dengue virus. Unusually potent antibodies that neutralize human cytomegalovirus (HCMV) were isolated and their epitopes mapped to a pentameric glycoprotein complex, which is currently tested as a candidate vaccine. The most striking examples are antibodies with exceptional breadth, being able to neutralize all influenza A viruses and even four different paramyxoviruses (18,19). The methods to isolate human monoclonal antibodies developed by Lanzavecchia have realized a long-sought goal: the full exploitation of the human immune response for serotherapy and vaccine design. These fully human monoclonal antibodies can be used not only as drugs for prophylaxis and therapy of infectious diseases, but also as tools to identify vaccine candidates, a process defined as “analytic vaccinology” (20). The present work in Lanzavecchia’s laboratory addresses fundamental issues on the role of somatic mutations and the pathways leading to the development of broadly neutralizing antibodies and explores the relationship between infection and autoimmunity (21).
Awards and honors
- Italian Society for Immunology (GCI, SIICA), since 1980
- European Molecular Biology Organisation (EMBO), since 1988
- The Henry Kunkel Society
- Member of the Royal College of Physicians
- Schweizerische Gesellschaft für Allergologie und Immunologie, honorary member
- American Society for Immunology, honorary member
- National Academy of Sciences (NAS), since 2016
- Swiss Academy of Medical Sciences, honorary member since 2016
- Science: board of reviewing editors 1997-2005
- European Journal of Immunology: executive committee member
- Journal of Experimental Medicine: advisory editor
- Lanzavecchia A: Potent T Cell Modulating Molecules US2004/0162411 A1
- Lanzavecchia A: Monoclonal antibody production by EBV transformation of B cells WO2004076677
Special lectures and courses
- Art Stern Memorial Lecture, The Wistar Institute, Philadelphia, 1995
- Wellcome Visiting Professorship, St. Jude, Memphis 1999
- Heremans Lecture, University of Brussels, Belgium, 2000
- Grabar Lecture, French Society for Immunology, 2000
- The NIH Wednesday Afternoon Lecture, Bethesda, 2000
- Arthur Levin memorial Lecture, Guy’s King’s St. Thomas’ School of Medicine, London, 2000
- American Association of Immunology, Distinguished Lecture, 2001
- Guru at the Annual NIH Immunology Interest Group, Airlie, Virginia, 2002
- The Henry G. Kunkel Lecture, Johns Hopkins University, Baltimore, 2002
- Jack Pepys Lecture, British Society for Immunology, 2002
- Advanced Course in Immunology, Institute Pasteur, Paris, since 1992
- FEBS International Summer School on Immunology, Ionian Village, Greece, since 1998
- Lanzavecchia, A (1988). "Clonal sketches of the immune response". The EMBO Journal. 7 (10): 2945–51. PMC . PMID 3053159.
- Antonio Lanzavecchia's publications indexed by Google Scholar
- Sallusto, F.; Lanzavecchia, A (1994). "Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha". Journal of Experimental Medicine. 179 (4): 1109–18. doi:10.1084/jem.179.4.1109. PMC . PMID 8145033.
- Sallusto, F; Lenig, D; Förster, R; Lipp, M; Lanzavecchia, A (1999). "Two subsets of memory T lymphocytes with distinct homing potentials and effector functions". Nature. 401 (6754): 708–12. doi:10.1038/44385. PMID 10537110.
- Sallusto, F. (1995). "Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: Downregulation by cytokines and bacterial products". Journal of Experimental Medicine. 182 (2): 389–400. doi:10.1084/jem.182.2.389. PMC . PMID 7629501.
- National Academy of Sciences Members and Foreign Associates Elected, News from the National Academy of Sciences, National Academy of Sciences, May 3, 2016, retrieved 2016-05-14.