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Università della Svizzera italiana

Structure and function analysis of an antibody recognizing all influenza A subtypes

Kallewaard, Nicole L. ; Corti, Davide ; Collins, Patrick J. ; Neu, Ursula ; McAuliffe, Josephine M. ; Benjamin, Ebony ; Wachter-Rosati, Leslie ; Palmer-Hill, Frances J. ; Yuan, Andy Q. ; Walker, Philip A. ; Vorlaender, Matthias K. ; Bianchi, Siro ; Guarino, Barbara ; De Marco, Anna ; Vanzetta, Fabrizia ; Agatic, Gloria ; Foglierini, Mathilde ; Pinna, Debora ; Fernandez-Rodriguez, Blanca ; Fruehwirth, Alexander ; Silacci, Chiara ; Ogrodowicz, Roksana W. ; Martin, Stephen R. ; Sallusto, Federica ; Suzich, JoAnn A. ; Lanzavecchia, Antonio ; Zhu, Qing ; Gamblin, Steven J. ; Skehel, John J.

In: Cell, 2016, vol. 166, no. 3, p. 596-608

Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when...

Università della Svizzera italiana

A LAIR-1 insertion creates broadly reactive antibodies against malaria variant antigens

Tan, Joshua ; Pieper, Kathrin ; Piccoli, Luca ; Abdi, Abdirahman ; Tully, Claire Maria ; Foglierini Perez, Mathilde ; Geiger, Roger ; Jarrossay, David ; Maina Ndungu, Francis ; Wambua, Juliana ; Bejon, Philip ; Silacci Fregni, Chiara : Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland ; Fernandez-Rodriguez, Blanca ; Barbieri, Sonia ; Bianchi, Siro ; Marsh, Kevin ; Thathy, Vandana ; Corti, Davide ; Sallusto, Federica ; Bull, Peter ; Lanzavecchia, Antonio

In: Nature, 2016, vol. 529, p. 25 p

Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies1,2,3,4. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their...

Università della Svizzera italiana

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

Mele, Federico ; Fornara, Chiara ; Jarrossay, David ; Furione, Milena ; Arossa, Alessia ; Spinillo, Arsenio ; Lanzavecchia, Antonio ; Gerna, Giuseppe ; Sallusto, Federica ; Lilleri, Daniele

In: Plos one, 2017, vol. 12, no. 11, p. e0187731

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve...

Università della Svizzera italiana

Molecular signatures of immunity and immunogenicity in infection and vaccination

Haks, Mariëlle C. ; Bottazzi, Barbara ; Cecchinato, Valentina ; De Gregorio, Corinne ; Del Giudice, Giuseppe ; Kaufmann, Stefan H. E. ; Lanzavecchia, Antonio ; Lewis, David J. M. ; Maertzdorf, Jeroen ; Mantovani, Alberto ; Sallusto, Federica ; Sironi, Marina ; Uguccioni, Mariagrazia ; Ottenhoff, Tom H. M.

In: Frontiers in immunology, 2017, vol. 8, p. 1563

Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable...

Università della Svizzera italiana

Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

Hu, Dan ; Notarbartolo, Samuele ; Croonenborghs, Tom ; Patel, Bonny ; Cialic, Ron ; Yang, Tun-Hsiang ; Aschenbrenner, Dominik ; Andersson, Karin M. ; Gattorno, Marco ; Pham, Minh ; Kivisakk, Pia ; Pierre, Isabelle V. ; Lee, Youjin ; Kiani, Karun ; Bokarewa, Maria ; Tjon, Emily ; Pochet, Nathalie ; Sallusto, Federica ; Kuchroo, Vijay K. ; Weiner, Howard L.

In: Nature communications, 2017, vol. 8, p. 1600

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene...

Università della Svizzera italiana

Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Campana, Raffaela ; Moritz, Katharina ; Neubauer, Angela ; Huber, Hans ; Henning, Rainer ; Brodie, Tess M. ; Kaider, Alexandra ; Sallusto, Federica ; Wöhrl, Stefan ; Valenta, Rudolf

In: Scientific reports, 2017, vol. 7, p. 11657

The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two...

Università della Svizzera italiana

Influenza vaccination induces NK-cell-mediated type-II IFN response that regulates humoral immunity in an IL-6-dependent manner

Farsakoglu, Yagmur ; Palomino-Segura, Miguel ; Latino, Irene ; Zanaga, Silvia ; Chatziandreou, Nikolaos ; Pizzagalli, Diego Ulisse ; Rinaldi, Andrea ; Bolis, Marco ; Sallusto, Federica ; Stein, Jens V. ; Gonzalez, Santiago F.

In: Cell reports, 2019, vol. 26, no. 9, p. 2307-2315.e5

The role of natural killer (NK) cells in the immune response against vaccines is not fully understood. Here, we examine the function of infiltrated NK cells in the initiation of the inflammatory response triggered by inactivated influenza virus vaccine in the draining lymph node (LN). We observed that, following vaccination, NK cells are recruited to the interfollicular and medullary areas of...

Università della Svizzera italiana

Induction of potent neutralizing antibody responses by a designed protein nanoparticle accine for respiratory syncytial virus

Marcandalli, Jessica ; Fiala, Brooke ; Ols, Sebastian ; Perotti, Michela ; de van der Schueren, Willem ; Snijder, Joost ; Hodge, Edgar ; Benhaim, Mark ; Ravichandran, Rashmi ; Carter, Lauren ; Sheffler, Will ; Brunner, Livia ; Lawrenz, Maria ; Dubois, Patrice ; Lanzavecchia, Antonio ; Sallusto, Federica ; Lee, Kelly K. ; Veesler, David ; Correnti, Colin E. ; Stewart, Lance J. ; Baker, David ; Loré, Karin ; Perez, Laurent ; King, Neil P.

In: Cell, 2019, vol. 177, no. 6, p. 1420-1431.e17

Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein ...

Università della Svizzera italiana

PECAM-1 stabilizes blood-brain barrier integrity and favors paracellular T-Cell diapedesis across the blood-brain barrier during neuroinflammation

Wimmer, Isabella ; Tietz, Silvia ; Nishihara, Hideaki ; Deutsch, Urban ; Sallusto, Federica ; Gosselet, Fabien ; Lyck, Ruth ; Muller, William A. ; Lassmann, Hans ; Engelhardt, Britta

In: Frontiers in immunology, 2019, vol. 10, p. 711

Breakdown of the blood-brain barrier (BBB) and increased immune cell trafficking into the central nervous system (CNS) are hallmarks of the pathogenesis of multiple sclerosis (MS). Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is expressed on cells of the vascular compartment and regulates vascular integrity and immune cell trafficking. Involvement of PECAM-1 in MS pathogenesis...

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)...