Antonio Lanzavecchia

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Antonio Lanzavecchia
Antonio Lanzavecchia2.jpg
Born (1951-10-09) 9 October 1951 (age 73)
Varese, Italy
Alma mater University 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
Fields Immunology
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
Website INGM

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]

Contents

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

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]

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.

<span class="mw-page-title-main">Monoclonal antibody</span> Antibodies from clones of the same blood cell

A monoclonal antibody is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.

<span class="mw-page-title-main">Hemagglutinin (influenza)</span> Hemagglutinin of influenza virus

Influenza hemagglutinin (HA) or haemagglutinin[p] is a homotrimeric glycoprotein found on the surface of influenza viruses and is integral to its infectivity.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in humans

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

The following are notable events in the Timeline of immunology:

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."

<span class="mw-page-title-main">Antibody-dependent enhancement</span> Antibodies rarely making an infection worse instead of better

Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication. The suboptimal antibodies can result from natural infection or from vaccination. ADE may cause enhanced respiratory disease, but is not limited to respiratory disease. It has been observed in HIV, RSV, and Dengue virus and is monitored for in vaccine development.

<span class="mw-page-title-main">Cancer immunology</span> Study of the role of the immune system in cancer

Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.

A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzheimer's disease.

<span class="mw-page-title-main">CD 205</span> Protein-coding gene in the species Homo sapiens

CD205 also called Lymphocyte antigen 75 is a protein that in humans is encoded by the LY75 gene.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

<span class="mw-page-title-main">Michel C. Nussenzweig</span> Brazilian immunologist (born 1955)

Michel C. Nussenzweig is a professor and head of the Laboratory of Molecular Immunology at The Rockefeller University and a Howard Hughes Medical Institute investigator. He is a member of both the US National Academy of Medicine and the US National Academy of Sciences.

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. 1 2 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.
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