Antonio Lanzavecchia

Career

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.

Research

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

Editorial activities

Patents

Special lectures and courses

Publications

Lanzavecchia has a total of 272 publications in peer reviewed scientific journals, with a total of 63,405 citations (h-index=109). A complete list can be found on Google Scholar.