Antonio Lanzavecchia

Antonio Lanzavecchia
Born (1951-10-09) 9 October 1951 (age 73)
Varese, Italy
Alma materUniversity of Pavia
Known forHis work in human immunology (T-cell B-cell cooperation, antigen processing and presentation, dendritic cell biology, lymphocyte activation and traffic, immunological memory and human monoclonal antibodies).
Awards
Scientific career
FieldsImmunology
InstitutionsIstituto Nazionale di Genetica Molecolare (INGM) “Romeo ed Enrica Invernizzi” Milan
Institute for Research in Biomedicine in Bellinzona
Professor, D-BIOL, ETH-Zurich
Basel Institute for Immunology
University of Genoa
WebsiteINGM

Antonio Lanzavecchia (born in Varese 9 October 1951) is an Italian and Swiss immunologist. As a fellow of Collegio Borromeo he obtained a degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases. He is Head Human Immunology Program, Istituto Nazionale di Genetica Molecolare-INGM, Milan and SVP Senior research Fellow, Humabs/Vir Biotechnology,[1] Bellinzona and San Francisco (USA). Since 2017, he is also Professor at the Faculty of Biomedical Sciences of the Università della Svizzera italiana (USI).[2]

Career

Since 1980 Lanzavecchia's laboratory developed robust methods to study human T and B cells in vitro, first at the University of Genoa, then at the Basel Institute for Immunology and, from 1999 to 2020 at the Institute for Research in Biomedicine in Bellinzona, of which he was the founding Director. He has been teaching Immunology at the University of Genoa and the University of Siena and from 2009 to 2017 has been Professor of Human Immunology at the Swiss Federal Institute of Technology Zurich. Following Google Scholar, Lanzavecchia has an h-index of 162 (As of 2023).[3]

Research

Starting in the early Eighties, Lanzavecchia has contributed to the advancement of human immunology in three distinct fields: i) antigen presentation and dendritic cell biology; ii) lymphocyte activation and immunological memory and iii) human monoclonal antibodies. In 1985, using antigen-specific T and B cell clones, Lanzavecchia demonstrated that B cells efficiently capture, process and present antigen to T helper cells ([4]). This study uncovered a critical step in the process of T-B cell cooperation that is essential for high affinity antibody production and is the basis for the development of glycoconjugate vaccines.

He also studied the role of HLA class II molecules as receptors for self, versus foreign peptides (,[5][6]) and the role of inflammatory stimuli in promoting antigen presentation by antigen-presenting cells ([7]).

In 1994 Sallusto and Lanzavecchia 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. Taking advantage of such immature dendritic cells, they characterized in detail the maturation process and identified the microbial and endogenous stimuli that trigger dendritic cell maturation (,[9][10]).

In the late Nineties the Lanzavecchia laboratory determined the mechanism, stoichiometry and kinetics of T cell receptor stimulation and signaling (,[11][12][13]) and discovered a fundamental division of memory T cells into two major subsets of central memory and effector memory and central T cells that play distinct roles in immediate protection and secondary immune responses ([14]).

Starting in 2003, the laboratory developed efficient methods to isolate human monoclonal antibodies as new tools for prophylaxis and therapy of infectious diseases ([15]). Among these is FI6 that neutralizes all influenza A viruses ([16]), MPE8 that neutralizes four different paramyxoviruses ([17]) and mab114 (Ansuvimab) that has been approved for treatment of Ebola infected patients ([18]).

The laboratory also pioneered the use of human monoclonal antibodies as tools for vaccine design, a process dubbed as “analytic vaccinology” (,[19][20]). Basic studies addressed the role of somatic mutations in the development of broadly neutralizing antibodies ([21]) and the relationship between infection and autoimmunity ([22]). The study of the antibody response to the malaria parasite led to the discovery of a new mechanism of antibody diversification through the insertion into antibody genes of DNA encoding pathogen receptors such as LAIR1 ([23][24]).

In 2021, Lanzavecchia and colleagues developed a vaccine that protects animals from Salmonella.[25] Recent highly cited work on Covid-19 analyzes the sensitivity of the virus to mRNA vaccine-elicited antibodies[26] and the receptor-binding domain of the SARS-CoV-2 Omicron variant.[27]

Awards

Honors

Editorial activities

Selected Patents

  • Monoclonal antibody production by EBV transformation of B cells (WO2004076677)
  • Human cytomegalovirus neutralizing antibodies and use thereof (WO2008084410)
  • Neutralizing anti-influenza virus antibodies and uses thereof (WO2010010467)
  • Methods for producing antibodies from plasma cells (WO2010046775)

Selected publications

As of 2023, Lanzavecchia has over 355 publications in peer reviewed scientific journals, with a total of over 130,000 citations (h-index=162). A complete list can be found on Google Scholar.[3]

References

  1. ^ Business Wire (18 December 2016). Vir Biotechnology Appoints Leading Immunologist Antonio Lanzavecchia, M.D., Senior Vice President, Senior Research Fellow. Businesswire. Accessed August 2021.
  2. ^ Profile: Antoni Lanazavecchia (2017). Biography. Università della Svizzera italiana. Accessed August 2021.
  3. ^ a b Antonio Lanzavecchia publications indexed by Google Scholar
  4. ^ Lanzavecchia, A. (1985). "Antigen-specific interaction between T and B cells". Nature. 314 (6011): 537–539. Bibcode:1985Natur.314..537L. doi:10.1038/314537a0. PMID 3157869. S2CID 4366150.
  5. ^ Lanzavecchia, A.; Reid, P.A.; Watts, C. (1985). "Irreversible association of peptides with class II MHC molecules in living cells". Nature. 357 (6375): 249–252. doi:10.1038/357249a0. PMID 1375347. S2CID 4229494.
  6. ^ Panina-Bordignon, P.; Corradin, G.; Roosnek, E.; Sette, A.; Lanzavecchia, A. (1991). "Recognition by class II alloreactive T cells of processed determinants from human serum proteins". Science. 252 (5012): 1548–1550. Bibcode:1991Sci...252.1548P. doi:10.1126/science.1710827. PMID 1710827. S2CID 319466.
  7. ^ Cella, M.; Engering, A.; Pinet, V.; Pieters, J.; Lanzavecchia, A. (1997). "Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells". Nature. 388 (6644): 782–787. Bibcode:1997Natur.388..782C. doi:10.1038/42030. PMID 9285591. S2CID 4391122.
  8. ^ Sallusto, F.; Lanzavecchia, A. (1994). "Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus iuterleukin 4 and downregulated by tumor necrosis factor α." J. Exp. Med. 179 (4): 1109–1118. doi:10.1084/jem.179.4.1109. PMC 2191432. PMID 8145033.
  9. ^ Sallusto, F.; Cella, M.; Danieli, C.; Lanzavecchia, A. (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". J. Exp. Med. 182 (2): 389–400. doi:10.1084/jem.182.2.389. PMC 2192110. PMID 7629501.
  10. ^ Napolitani, G.; Rinaldi, A.; Bertoni, F.; Sallusto, F.; Lanzavecchia, A. (2005). "Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1 -polarizing program in dendritic cells". Nat. Immunol. 6 (8): 769–776. doi:10.1038/ni1223. PMC 3760217. PMID 15995707.
  11. ^ Valitutti, S.; Miller, S.; Cella, M.; Padovan, E.; Lanzavecchia, A. (1995). "Serial triggering of many T-cell receptors by a few peptide-MHC complexes". Nature. 375 (6527): 148–151. Bibcode:1995Natur.375..148V. doi:10.1038/375148a0. PMID 7753171. S2CID 4252790.
  12. ^ Viola, A.; Lanzavecchia, A. (1996). "T cell activation determined by T cell receptor number and tunable thresholds". Science. 273 (5271): 104–106. Bibcode:1996Sci...273..104V. doi:10.1126/science.273.5271.104. PMID 8658175. S2CID 45276598.
  13. ^ Viola, A.; Schroeder, S.; Sakakibara, S.; Lanzavecchia, A. (1999). "T lymphocyte costimulation mediated by reorganization of membrane microdomains". Science. 283 (5402): 680–682. Bibcode:1999Sci...283..680V. doi:10.1126/science.283.5402.680. PMID 9924026.
  14. ^ 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): 708–712. Bibcode:1999Natur.401..708S. doi:10.1038/44385. PMID 10537110. S2CID 4378970.
  15. ^ Traggiai, E.; et al. (2004). "An efficient method to make human monoclonal antibodies from memory B cells: Potent neutralization of SARS coronavirus". Nat. Med. 10 (8): 871–875. doi:10.1038/nm1080. PMC 7095806. PMID 15247913.
  16. ^ Corti, D.; et al. (2011). "A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins". Science. 333 (6044): 850–856. Bibcode:2011Sci...333..850C. doi:10.1126/science.1205669. PMID 21798894. S2CID 5086468.
  17. ^ Corti, D.; et al. (2013). "Cross-neutralization of four paramyxoviruses by a human monoclonal antibody". Nature. 501 (7467): 439–443. Bibcode:2013Natur.501..439C. doi:10.1038/nature12442. PMID 23955151. S2CID 205235089.
  18. ^ Corti, D.; et al. (2016). "Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody". Science. 351 (6279): 1339–1342. Bibcode:2016Sci...351.1339C. doi:10.1126/science.aad5224. PMID 26917593.
  19. ^ Kabanova, A.; et al. (2014). "Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies". Proc. Natl. Acad. Sci. U.S.A. 111 (50): 17965–17970. Bibcode:2014PNAS..11117965K. doi:10.1073/pnas.1415310111. PMC 4273412. PMID 25453106.
  20. ^ Tan, J.; et al. (2018). "A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein". Nat. Med. 24 (4): 401–407. doi:10.1038/nm.4513. PMC 5893353. PMID 29554084.
  21. ^ Pappas, L.; et al. (2014). "Rapid development of broadly influenza neutralizing antibodies through redundant mutations". Nature. 516 (7531): 418–422. Bibcode:2014Natur.516..418P. doi:10.1038/nature13764. PMID 25296253. S2CID 1984683.
  22. ^ Di Zenzo, G.; et al. (2012). "Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface". J. Clin. Invest. 122 (10): 3781–3790. doi:10.1172/JCI64413. PMC 3461925. PMID 22996451.
  23. ^ Tan, J.; et al. (2016). "A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens". Nature. 529 (7584): 105–109. Bibcode:2016Natur.529..105T. doi:10.1038/nature16450. PMC 4869849. PMID 26700814.
  24. ^ Pieper, K.; et al. (2017). "Public antibodies to malaria antigens generated by two LAIR1 insertion modalities". Nature. 548 (7669): 597–601. Bibcode:2017Natur.548..597P. doi:10.1038/nature23670. PMC 5635981. PMID 28847005.
  25. ^ Science News (2 June 2021). Luring bacteria into a trap. ScienceDaily. Accessed August 2021.
  26. ^ Collier, Dami A.; et al. (2021). "Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies". Nature. 593: 136–141.
  27. ^ Cameroni, Elisabetta; et al. (2022). "Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift". Nature. 602 (7898): 664–670.
  28. ^ "Laureate Prof. Antonio Lanzavecchia, M.D." Jung Stiftung (in German). Retrieved 28 November 2021.