Dissecting human immune responses to pathogens and vaccines
My laboratory investigates the mechanisms of antibody-mediated resistance to infectious diseases. Using high-throughput cellular screens we isolated potent and broadly neutralizing antibodies that can be used for prophylaxis and treatment of infectious diseases and as tools for vaccine design. We also addressed fundamental aspects of the antibody response, such as the role of somatic mutations in affinity maturation and the relationship between infection and autoimmunity. Recently, while studying the antibody response to the malaria parasite, we discovered a new type of antibodies generated by the insertion of genomic DNA encoding pathogen receptors into antibody genes. In INGM laboratory, we will combine cellular and molecular approaches to gain fundamental insights into the organization and dynamics of human memory B cell repertoires and will explore new strategies to engineer antibodies and B cells to improve and exploit their therapeutic efficacy. This work will be mainly supported by the ERC grant ENGRAB “Antibody engineering by natural selection and by design”.
Projects
- The organization and dynamics of human memory B cell repertoires
- Antibody diversification through templated insertions: receptor-based antibodies and beyond
- Dissecting the antibody response to SARS-CoV-2
- Antibody-guided vaccine design
- Lymphocyte engineering using gene knock-out and knock-in approaches
Publications (selected, last 10 years)
- A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients.
Cassotta A, Mikol V, Bertrand T, Pouzieux S, Le Parc J, Ferrari P, Dumas J, Auer M, Deisenhammer F, Gastaldi M, Franciotta D, Silacci-Fregni C, Fernandez Rodriguez B, Giacchetto-Sasselli I, Foglierini M, Jarrossay D, Geiger R, Sallusto F, Lanzavecchia A, Piccoli L.
Nat Med. 2019 Sep;25(9):1402-1407. doi: 10.1038/s41591-019-0568-2. - Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.
Marcandalli J, Fiala B, Ols S, Perotti M, de van der Schueren W, Snijder J, Hodge E, Benhaim M, Ravichandran R, Carter L, Sheffler W, Brunner L, Lawrenz M, Dubois P, Lanzavecchia A, Sallusto F, Lee KK, Veesler D, Correnti CE, Stewart LJ, Baker D, Loré K, Perez L, King NP.
Cell. 2019 Mar 7;176(6):1420-1431.e17. doi: 10.1016/j.cell.2019.01.046. - Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations.
Lee J, Paparoditis P, Horton AP, Frühwirth A, McDaniel JR, Jung J, Boutz DR, Hussein DA, Tanno Y, Pappas L, Ippolito GC, Corti D, Lanzavecchia A, Georgiou G.
Cell Host Microbe. 2019 Mar 13;25(3):367-376.e5. doi: 10.1016/j.chom.2019.01.010. Epub 2019 Feb 19. - Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion.
Walls AC, Xiong X, Park YJ, Tortorici MA, Snijder J, Quispe J, Cameroni E, Gopal R, Dai M, Lanzavecchia A, Zambon M, Rey FA, Corti D, Veesler D.
Cell. 2019 Feb 21;176(5):1026-1039.e15. doi: 10.1016/j.cell.2018.12.028. Epub 2019 Jan 31. - The Antibody Response to Plasmodium falciparum: Cues for Vaccine Design and the Discovery of Receptor-Based Antibodies.
Tan J, Piccoli L, Lanzavecchia A.
Annu Rev Immunol. 2019 Apr 26;37:225-246. doi: 10.1146/annurev-immunol-042617-053301. Epub 2018 Dec 19. Review. - Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1-4.
Stewart-Jones GBE, Chuang GY, Xu K, Zhou T, Acharya P, Tsybovsky Y, Ou L, Zhang B, Fernandez-Rodriguez B, Gilardi V, Silacci-Fregni C, Beltramello M, Baxa U, Druz A, Kong WP, Thomas PV, Yang Y, Foulds KE, Todd JP, Wei H, Salazar AM, Scorpio DG, Carragher B, Potter CS, Corti D, Mascola JR, Lanzavecchia A, Kwong PD.
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12265-12270. doi: 10.1073/pnas.1811980115. Epub 2018 Nov 12. - An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor.
Martinez-Martin N, Marcandalli J, Huang CS, Arthur CP, Perotti M, Foglierini M, Ho H, Dosey AM, Shriver S, Payandeh J, Leitner A, Lanzavecchia A, Perez L, Ciferri C.
Cell. 2018 Aug 23;174(5):1158-1171.e19. doi: 10.1016/j.cell.2018.06.028. Epub 2018 Jul 26. - A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein.
Tan, J., B.K. Sack, D. Oyen, I. Zenklusen, L. Piccoli, S. Barbieri, M. Foglierini, C.S. Fregni, J. Marcandalli, S. Jongo, S. Abdulla, L. Perez, G. Corradin, L. Varani, F. Sallusto, B.K.L. Sim, S.L. Hoffman, S.H.I. Kappe, C. Daubenberger, I.A. Wilson, and A. Lanzavecchia.
Nat Med. 2018 24:401-407 doi:10.1038/nm.4513. - Public antibodies to malaria antigens generated by two LAIR1 insertion modalities.
Pieper, K., J. Tan, L. Piccoli, M. Foglierini, S. Barbieri, Y. Chen, C. Silacci Fregni, T. Wolf, D. Jarrossay, M. Anderle, A. Abdi, F.M. Ndungu, O.K. Doumbo, B. Traore, T.M. Tran, S. Jongo, I. Zenklusen, P.D. Crompton, C. Daubenberger, P.C. Bull, F. Sallusto, and A. Lanzavecchia..
Nature 2017. 548:597-601. doi:10.1038/nature23670. - L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.
Geiger, R., J.C. Rieckmann, T. Wolf, C. Basso, Y. Feng, T. Fuhrer, M. Kogadeeva, P. Picotti, F. Meissner, M. Mann, N. Zamboni, F. Sallusto, and A. Lanzavecchia.
Cell 2016 167:829-842. - Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes
Kallewaard, N.L., D. Corti, P.J. Collins, U. Neu, J.M. McAuliffe, E. Benjamin, L. Wachter-Rosati, F.J. Palmer-Hill, A.Q. Yuan, P.A. Walker, M.K. Vorlaender, S. Bianchi, B. Guarino, A. De Marco, F. Vanzetta, G. Agatic, M. Foglierini, D. Pinna, B. Fernandez-Rodriguez, A. Fruehwirth, C. Silacci, R.W. Ogrodowicz, S.R. Martin, F. Sallusto, J.A. Suzich, A. Lanzavecchia, Q. Zhu, S.J. Gamblin, and J.J. Skehel
Cell. 2016 166: 596-608. - Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection
Stettler, K., M. Beltramello, D.A. Espinosa, V. Graham, A. Cassotta, S. Bianchi, F. Vanzetta, A. Minola, S. Jaconi, F. Mele, M. Foglierini, M. Pedotti, L. Simonelli, S. Dowall, B. Atkinson, E. Percivalle, C.P. Simmons, L. Varani, J. Blum, F. Baldanti, E. Cameroni, R. Hewson, E. Harris, A. Lanzavecchia, F. Sallusto, and D. Corti.
Science 2016, 353: 823-26. - Protective Monotherapy Against Lethal Ebola Virus Infection by a Potently Neutralizing Antibody.
Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ.
Science 351: 1339-42. - A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens.
Tan J, Pieper K, Piccoli L, Abdi A, Foglierini M, Geiger R, Tully CM, Jarrossay D, Ndungu FM, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P, Lanzavecchia A.
Nature 2016 529:105-109 - Prophylactic and postexposure efficacy of a potent human monoclonal antibody against MERS coronavirus.
Corti D, Zhao J, Pedotti M, Simonelli L, Agnihothram S, Fett C, Fernandez-Rodriguez B, Foglierini M, Agatic G, Vanzetta F, Gopal R, Langrish CJ, Barrett NA, Sallusto F, Baric RS, Varani L, Zambon M, Perlman S, Lanzavecchia A.
Proc Natl Acad Sci U S A 2016. 112: 10473-8 - Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis.
Piccoli L, Campo I, Fregni CS, Rodriguez BM, Minola A, Sallusto F, Luisetti M, Corti D, Lanzavecchia A.
Nat Commun 2015. 6: 7375 - T cell immunity. Functional heterogeneity of human memory CD4(+) T cell clones primed by pathogens or vaccines.
Becattini S, Latorre D, Mele F, Foglierini M, De Gregorio C, Cassotta A, Fernandez B, Kelderman S, Schumacher TN, Corti D, Lanzavecchia A, Sallusto F.
Science 2015. 347: 400-6 - Rapid development of broadly influenza neutralizing antibodies through redundant mutations.
Pappas L, Foglierini M, Piccoli L, Kallewaard NL, Turrini F, Silacci C, Fernandez-Rodriguez B, Agatic G, Giacchetto-Sasselli I, Pellicciotta G, Sallusto F, Zhu Q, Vicenzi E, Corti D, Lanzavecchia A.
Nature 2014 516: 418-22 - Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies.
Kabanova A, Perez L, Lilleri D, Marcandalli J, Agatic G, Becattini S, Preite S, Fuschillo D, Percivalle E, Sallusto F, Gerna G, Corti D, Lanzavecchia A.
Proc Natl Acad Sci U S A 2014. 111: 17965-70 - Broadly neutralizing antiviral antibodies.
Corti D, Lanzavecchia A.
Annu Rev Immunol 2013 31: 705-42 - Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.
Corti D, Bianchi S, Vanzetta F, Minola A, Perez L, Agatic G, Guarino B, Silacci C, Marcandalli J, Marsland BJ, Piralla A, Percivalle E, Sallusto F, Baldanti F, Lanzavecchia A.
Nature 2013. 501: 439-43 - Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype.
Baumjohann D, Preite S, Reboldi A, Ronchi F, Ansel KM, Lanzavecchia A, Sallusto F.
Immunity 2013 38: 596-605 - Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta.
Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, Monticelli S, Lanzavecchia A, Sallusto F.
Nature 2012. 484: 514-8 - Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation.
Lindesmith LC, Beltramello M, Donaldson EF, Corti D, Swanstrom J, Debbink K, Lanzavecchia A, Baric RS.
PLoS Pathog 2012. 8: e1002705 - Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface.
Di Zenzo G, Di Lullo G, Corti D, Calabresi V, Sinistro A, Vanzetta F, Didona B, Cianchini G, Hertl M, Eming R, Amagai M, Ohyama B, Hashimoto T, Sloostra J, Sallusto F, Zambruno G, Lanzavecchia A.
J Clin Invest 2012. 122: 3781-90 - A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins.
Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, Vachieri SG, Pinna D, Minola A, Vanzetta F, Silacci C, Fernandez-Rodriguez BM, Agatic G, Bianchi S, Giacchetto-Sasselli I, Calder L, Sallusto F, Collins P, Haire LF, Temperton N, Langedijk JP, Skehel JJ, Lanzavecchia A.
Science 2011. 333: 850-6 - Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex.
Macagno A, Bernasconi NL, Vanzetta F, Dander E, Sarasini A, Revello MG, Gerna G, Sallusto F, Lanzavecchia A.
J Virol 2010. 84: 1005-13 - Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine.
Corti D, Suguitan AL, Jr., Pinna D, Silacci C, Fernandez-Rodriguez BM, Vanzetta F, Santos C, Luke CJ, Torres-Velez FJ, Temperton NJ, Weiss RA, Sallusto F, Subbarao K, Lanzavecchia A.
J Clin Invest 2010. 120: 1663-73
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