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

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

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41

Sabin, Charles ; Corti, Davide ; Buzon, Victor ; Seaman, Mike S. ; Hulsik, David Lutje ; Hinz, Andreas ; Vanzetta, Fabrizia ; Agatic, Gloria ; Silacci, Chiara ; Mainetti, Lara ; Scarlatti, Gabriella ; Sallusto, Federica ; Weiss, Robin ; Lanzavecchia, Antonio ; Weissenhorn, Winfried

In: Plos pathogens, 2010, vol. 6, no. 11, p. e1001195

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 A° resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a...

Università della Svizzera italiana

Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine

Corti, Davide ; Suguitan Jr., Amorsolo ; Pinna, Debora ; Silacci, Chiara ; Fernandez-Rodriguez, Blanca M. ; Vanzetta, Fabrizia ; Santos, Celia ; Luke, Catherine J. ; Torres-Velez, Fernando J. ; Temperton, Nigel J. ; Weiss, Robin A. ; Sallusto, Federica ; Subbarao, Kanta ; Lanzavecchia, Antonio

In: The Journal of clinical investigation, 2010, vol. 120, no. 5, p. 1663-1673

The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1–H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic...

Università della Svizzera italiana

Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals

Corti, Davide ; Langedijk, Johannes P. M. ; Hinz, Andreas ; Seaman, Michael S. ; Vanzetta, Fabrizia ; Fernandez-Rodriguez, Blanca M. ; Silacci, Chiara ; Pinna, Debora ; Jarrossay, David ; Balla-Jhagjhoorsingh, Sunita ; Willems, Betty ; Zekveld, Maria J. ; Dreja ; O’Sullivan, Eithne ; Pade, Corinna ; Orkin, Chloe ; Jeffs, Simon A. ; Montefiori, David C. ; David, Davis ; Weissenhorn, Winfried ; McKnight, Aine ; Heeney, Jonathan L. ; Sallusto, Federica ; Sattentau, Quentin J. ; Weiss, robin A. ; Lanzavecchia, Antonio

In: Plos one, 2010, vol. 5, no. 1, p. e8805

Background The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. Methods and Findings We immortalized IgG+ memory B cells from individuals infected with...

Università della Svizzera italiana

Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex

Macagno, Annalisa ; Bernasconi, Nadia L. ; Vanzetta, Fabrizia ; Dander, Erica ; Sarasini, Antonella ; Revello, Maria Grazia ; Gerna, Giuseppe ; Sallusto, Federica ; Lanzavecchia, Antonio

In: Journal of Virology, 2010, vol. 84, no. 2, p. 1005-1013

Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immunocompromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC90] values ranging from 5 to 200 pM) HCMV infection of...