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Università della Svizzera italiana

Development of broad‐spectrum human monoclonal antibodies for rabies post‐exposure prophylaxis

De Benedictis, Paola ; Minola, Andrea ; Rota Nodari, Elena ; Aiello, Roberta ; Zecchin, Barbara ; Salomoni, Angela ; Foglierini, Mathilde ; Agatic, Gloria ; Vanzetta, Fabrizia ; Lavenir, Rachel ; Lepelletier, Anthony ; Bentley, Emma ; Weiss, Robin ; Cattoli, Giovanni ; Capua, Ilaria ; Sallusto, Federica ; Wright, Edward ; Lanzavecchia, Antonio ; Bourhy, Hervé ; Corti, Davide

In: EMBO molecular medicine, 2016, vol. 8, no. 4, p. 407-421

Currently available rabies post‐exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a...

Università della Svizzera italiana

Serum immunoglobulin a cross-strain blockade of human noroviruses

Lindesmith, Lisa C. ; Beltramello, Martina ; Swanstrom, Jesica ; Jones, Taylor A. ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Open forum infectious diseases, 2015, vol. 2, no. 3, p. ofv084

Background: Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods: Immunoglobulin (Ig)A was purified...

Università della Svizzera italiana

Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

Piccoli, Luca ; Campo, Ilaria ; Fregni, Chiara Silacci ; Fernandez Rodriguez, Blanca Maria ; Minola, Andrea ; Sallusto, Federica ; Luisetti, Maurizio ; Corti, Davide ; Lanzavecchia, Antonio

In: Nature communications, 2015, vol. 6, p. 7375

Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF...

Università della Svizzera italiana

The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep ; Gach, Johannes S. ; Becerra, Juan C. ; Phan, Tran B. ; Pudney, Jeffrey ; Moldoveanu, Zina ; Joseph, Sarah B. ; Landucci, Gary ; Supnet, Medalyn Jude ; Ping, Li-Hua ; Corti, Davide ; Moldt, Brian ; Hel, Zdenek ; Lanzavecchia, Antonio ; Ruprecht, Ruth M. ; Burton, Dennis R. ; Mestecky, Jiri ; Anderson, Deborah J. ; Forthal, Donald N.

In: Plos pathogens, 2013, vol. 9, no. 11, p. e1003776

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env- specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis...

Università della Svizzera italiana

The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody

Balla-Jhagjhoorsingh, Sunita S. ; Corti, Davide ; Heyndrickx, Leo ; Willems, Elisabeth ; Vereecken, Katleen ; Davis, David ; Vanham, Guido

In: Plos one, 2013, vol. 8, no. 7, p. e68863

Immunogen design for HIV-1 vaccines could be based on epitope identification of naturally occurring neutralizing antibodies in infected patients. A tier 2 neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4 binding site (CD4bs) region that only partially overlaps with the b12 epitope. We aimed to identify the critical binding site by resistance induction in a...

Università della Svizzera italiana

Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone

Pickett, Julie E. ; Thompson, John M. ; Sadowska, Agnieszka ; Tkaczyk, Christine ; Sellman, Bret R. ; Minola, Andrea ; Corti, Davide ; Lanzavecchia, Antonio ; Miller, Lloyd S. ; Thorek, Daniel LJ

In: Bone research, 2018, vol. 6, p. 13

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in...

Università della Svizzera italiana

Fetal human cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection

Lilleri, Daniele ; Kabanova, Anna ; Revello, Maria Grazia ; Percivalle, Elena ; Sarasini, Antonella ; Genini, Emilia ; Sallusto, Federica ; Lanzavecchia, Antonio ; Corti, Davide ; Gerna, Giuseppe

In: Plos one, 2013, vol. 8, no. 3, p. e59863

Primary human cytomegalovirus (HCMV) infections during pregnancy are associated with a high risk of virus transmission to the fetus. To identify correlates of intrauterine HCMV transmission, serial serum samples from HCMV transmitter and non-transmitter pregnant women with primary HCMV infection were analyzed for the presence of neutralizing antibodies against different glycoproteins and...

Università della Svizzera italiana

The human transmembrane protease serine 2 is necessary for the production of group 2 influenza A virus pseudotypes

Ferrara, Francesca ; Molesti, Eleonora ; Böttcher-Friebertshäuser, Eva ; Cattoli, Giovanni ; Corti, Davide ; Scott, Simon D. ; Temperton, Nigel J.

In: Journal of molecular and genetic medicine, 2013, vol. 7, p. 309-314

The monomer of influenza haemagglutinin is synthesized as a single polypeptide precursor that during maturation is cleaved by proteases into two active subunits. Other studies have demonstrated that the human Transmembrane Protease Serine 2 (TMPRSS2) can cleave the HA of human seasonal influenza viruses. Consequently, we have investigated the use of human Transmembrane Protease Serine 2 to...

Università della Svizzera italiana

Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface

Di Zenzo, Giovanni ; Di Lullo, Giulia ; Corti, Davide ; Calabresi, Valentina ; Sinistro, Anna ; Vanzetta, Fabrizia ; Didona, Biagio ; Cianchini, Giuseppe ; Hertl, Michael ; Eming, Rudiger ; Amagai, Masayuki ; Ohyama, Bungo ; Hashimoto, Takashi ; Sloostra, Jerry ; Sallusto, Federica ; Zambruno, Giovanna ; Lanzavecchia, Antonio

In: The journal of clinical investigation, 2012, vol. 122, no. 10, p. 3781-3790

Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3 and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3 from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro,...

Università della Svizzera italiana

Immunogenetic mechanisms driving norovirus GII.4 antigenic variation

Lindesmith, Lisa C. ; Beltramello, Martina ; Donaldson, Eric F. ; Corti, Davide ; Swanstrom, Jesica ; Debbink, Kari ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Plos pathogens, 2012, vol. 8, no. 5, p. e1002705

Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal...