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Università della Svizzera italiana

Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition

Amara, Khaled ; Steen, Johanna ; Murray, Fiona ; Morbach, Henner ; Fernandez-Rodriguez, Blanca M. ; Joshua, Vijay ; Engström, Marianne ; Snir, Omri ; Israelsson, Lena ; Catrina, Anca I. ; Wardemann, Hedda ; Corti, Davide ; Meffre, Eric ; Klareskog, Lars ; Malmström, Vivianne

In: The journal of experimental medicine, 2013, vol. 210, no. 3, p. 445-455

Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class...

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

Characterization of neutralizing profiles in HIV-1 infected patients from whom the HJ16, HGN194 and HK20 mAbs were obtained

Balla-Jhagjhoorsingh, Sunita S. ; Willems, Betty ; Heyndrickx, Liesbeth ; Heyndrickx, Leo ; Vereecken, Katleen ; Janssens, Wouter ; Seaman, Michael S. ; Corti, Davide ; Lanzavecchia, Antonio ; Davis, David ; Vanham, Guido

In: Plos one, 2011, vol. 6, no. 10, p. e25488

Several new human monoclonal antibodies (mAbs) with a neutralizing potential across different subtypes have recently been described. Three mAbs, HJ16, HGN194 and HK20, were obtained from patients within the HIV-1 cohort of the Institute of Tropical Medicine (ITM). Our aim was to generate immunization antibodies equivalent to those seen in plasma. Here, we describe the selection and...

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

Influenza hemagglutinin membrane anchor

Benton, Donald J. ; Nans, Andrea ; Calder, Lesley J. ; Turner, Jack ; Neu, Ursula ; Lin, Yi Pu ; Ketelaars, Esther ; Kallewaard, Nicole L. ; Corti, Davide ; Lanzavecchia, Antonio ; Gamblin, Steven J. ; Rosenthal, Peter B. ; Skehel, John J.

In: Proceedings of the national academy of sciences of the United States of America, 2018, vol. 115, no. 40, p. 10112-10117

Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the “membrane anchor” portion of the...

Università della Svizzera italiana

Macrophage death following influenza vaccination initiates the inflammatory response that promotes dendritic cell function in the draining lymph node

Chatziandreou, Nikolaos ; Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; D’Antuono, Rocco ; Pizzagalli, Diego Ulisse ; Sallusto, Federica ; Lukacs-Kornek, Veronika ; Uguccioni, Mariagrazia ; Corti, Davide ; Turley, Shannon J. ; Lanzavecchia, Antonio ; Carroll, Michael C. ; Gonzalez, Santiago F.

In: Cell reports, 2017, vol. 18, no. 10, p. 2427-2440

The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7)...

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

Within-host evolution results in antigenically distinct GII.4 noroviruses

Debbink, Kari ; Lindesmith, Lisa C. ; Ferris, Martin T. ; Swanstrom, Jesica ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Journal of virology, 2014, vol. 88, no. 13, p. 7244–7255

Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic...