Daniele Lilleri, MD
UOC Laboratorio Genetica, Trapiantologia e Malattie cardiovascolari
Fondazione IRCCS Policlinico San Matteo
Viale Golgi 19
27100 Pavia, Italy
Daniele Lilleri received his MD from “Università degli Studi di Pavia” in 1998. He worked as a fellow at Viral Diagnostic Service, Fondazione IRCCS Policlinico San Matteo, Pavia from 1998 to 2003 and received the specialization diploma in Microbiology and Virology from “Università degli Studi di Milano” in 2003. He was research collaborator at Viral Diagnostic Service (2003-2010), then at Experimental Research Laboratories, Transplantation Area, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. He was also visiting scientist at Institute for Research in Biomedicine, Bellinzona, Switzerland (2010-2016). He held lectures for the School of Medicine and for the School of Specialization in Microbiology and Virology, “Facoltà di Medicina e Chirurgia, Università degli Studi di Pavia”. He received the 2007 European Society for Clinical Virology “Abbott Diagnostic Award” for original contributions in the field of viral diagnosis. His research activity was initially focused on the validation of molecular assays for diagnosis and monitoring of human cytomegalovirus (HCMV) infections in immunocompetent and immunocompromised subjects. He was principal investigator of the research project, granted from italian Ministry of Health: “Dissection of the immune response to human cytomegalovirus glycoprotein complexes: perspective for the development of a candidate subunit vaccine” and of the research project, funded by Fondazione Cariplo, Milano, Italy: “Human cytomegalovirus: prognostic factors of virus transmission to the fetus and congenital disease”. Currently he is coordinator of the research project “Pathogenesis and prevention of non-primary human citomegalovirus infection” funded by Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia, Italy).
Research Group Activity
The research group at Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, includes Daniele Lilleri (MD, principal investigator of the project), Chiara Fornara (biologist), Elisa Gabanti (biologist), Chiara Fornara (biologist), Milena Furione (MD, clinical virologist) and Alessia Arossa (MD, gynecologist). Prof. Giuseppe Gerna and Dr. Maria Grazia Revello, formerly leading the Viral Diagnostic Service at San Matteo and currently retired, are advisors of the group. Their work in the last decades led to the identification of main pathogenetic features of human cytomegalovirus (HCMV) infection and dissemination throughout the body.
Several aspects of HCMV infection and its interaction with the host’s immune response are investigated at San Matteo. One major interest of the group is the development of HCMV-specific humoral and cell-mediated immune responses in immunocompetent and immunocompromised subjects. The aim is to discover immune correlates of protection from i) HCMV transmission to the fetus during pregnancy and ii) HCMV disease in transplant recipients. More recently, a candidate subunit vaccine has been developed and analyzed in a pre-clinical stage in collaboration with the Institute for Research in Biomedicine, Bellinzona, Switzerland.
Within the CYMAF project, the research group at San Matteo will study the Fc-mediated functions (antibody-dependent cellular cytotoxicity, NK activation, complement deposition and phagocytosis) of anti-HCMV IgG antibodies (in collaboration with the Université Libre de Bruxelles-ULB) and the T follicular helper response in blood during primary HCMV infection.
Moreover, San Matteo will lead the analysis of the antibody response to HCMV in pregnant women transmitting or non-transmitting HCMV infection to the fetus, taking advantage of a biobank of samples collected in the past years as well as the enrollment of new cases of pregnancy complicated by primary HCMV infection. The aim is to detect an antibody signature of protection from virus transmission to the fetus.
Several aspects of the antibody response will be analysed: the level of IgG antibodies binding to HCMV surface glycoprotein complexes (gB, gHgLgO, gHgLpUL128-130-131); the neutralization of cell-free HCMV infection of epithelial/endothelial cells and fibroblasts; the inhibition of cell-to-cell spreading of HCMV; and the Fc-mediate antibody functions developed with ULB.
Mele F, Fornara C, Jarrossay D, Furione M, Arossa A, Spinillo A, Lanzavecchia A, Gerna G, Sallusto F, Lilleri D. Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy: IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission.
PLoS One. 2017;12:e0187731. doi: 10.1371/journal.pone.0187731.
Rev Med Virol. 2017;27. doi: 10.1002/rmv.1921.
Lilleri D, Gerna G, Furione M, Zavattoni M, Spinillo A. Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy.
J Clin Virol. 2016;81:16-24. doi: 10.1016/j.jcv.2016.05.007.
Gerna G, Percivalle E, Perez L, Lanzavecchia A, Lilleri D. Monoclonal Antibodies to Different Components of the Human Cytomegalovirus (HCMV) Pentamer gH/gL/pUL128L and Trimer gH/gL/gO as well as Antibodies Elicited during Primary HCMV Infection Prevent Epithelial Cell Syncytium Formation.
J Virol. 2016;90:6216-6223. doi: 10.1128/JVI.00121-16.
Fornara C, Furione M, Arossa A, Gerna G, Lilleri D. Comparative magnitude and kinetics of human cytomegalovirus-specific CD4⁺ and CD8⁺ T-cell responses in pregnant women with primary versus remote infection and in transmitting versus non-transmitting mothers: Its utility for dating primary infection in pregnancy.
J Med Virol. 2016;88:1238-46. doi: 10.1002/jmv.24449.
Furione M, Rognoni V, Sarasini A, Zavattoni M, Lilleri D, Gerna G, Revello MG. Slow increase in IgG avidity correlates with prevention of human cytomegalovirus transmission to the fetus.
J Med Virol. 2013;85:1960-7. doi: 10.1002/jmv.23691.
Lilleri D, Kabanova A, Revello MG, Percivalle E, Sarasini A, Genini E, Sallusto F, Lanzavecchia A, Corti D, Gerna G. Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection.
PLoS One. 2013;8:e59863. doi: 10.1371/journal.pone.0059863.
Lilleri D, Kabanova A, Lanzavecchia A, Gerna G. Antibodies against neutralization epitopes of human cytomegalovirus gH/gL/pUL128-130-131 complex and virus spreading may correlate with virus control in vivo.
J Clin Immunol. 2012;32:1324-31. doi: 10.1007/s10875-012-9739-3.
Fornara C, Lilleri D, Revello MG, Furione M, Zavattoni M, Lenta E, Gerna G. Kinetics of effector functions and phenotype of virus-specific and γδ T lymphocytes in primary human cytomegalovirus infection during pregnancy.
J Clin Immunol. 2011;31(6):1054-64. doi: 10.1007/s10875-011-9577-8.
Lilleri D, Fornara C, Revello MG, Gerna G. Human cytomegalovirus-specific memory CD8+ and CD4+ T cell differentiation after primary infection.
J Infect Dis. 2008;198:536-43. doi: 10.1086/590118.
Lilleri D, Fornara C, Furione M, Zavattoni M, Revello MG, Gerna G. Development of human cytomegalovirus-specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus.
J Infect Dis. 2007;195:1062-70.
Revello MG, Lilleri D, Zavattoni M, Furione M, Genini E, Comolli G, Gerna G. Lymphoproliferative response in primary human cytomegalovirus (HCMV) infection is delayed in HCMV transmitter mothers.
J Infect Dis. 2006;193:269-76.
Revello MG, Lilleri D, Zavattoni M, Stronati M, Bollani L, Middeldorp JM, Gerna G. Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women with primary infection and of congenitally infected newborns.
J Infect Dis. 2001;1841078-81.