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Università della Svizzera italiana

Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus

Sastry, Mallika ; Zhang, Baoshan ; Chen, Man ; Joyce, M. Gordon ; Kong, Wing-Pui ; Chuang, Gwo-Yu ; Ko, Kiyoon ; Kumar, Azad ; Silacci, Chiara ; Thom, Michelle ; Salazar, Andres M. ; Corti, Davide ; Lanzavecchia, Antonio ; Taylor, Geraldine ; Mascola, John R. ; Graham, Barney S. ; Kwong, Peter D.

In: Plos one, 2017, vol. 12, no. 10, p. e0186854

Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)—a highly prevalent childhood pathogen without a licensed vaccine—we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) “DS-Cav1” immunogen, which induced high titer...

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

Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae

Pennini, Meghan E. ; De Marco, Anna ; Pelletier, Mark ; Bonnell, Jessica ; Cvitkovic, Romana ; Beltramello, Martina ; Cameroni, Elisabetta ; Bianchi, Siro ; Zatta, Fabrizia ; Zhao, Wei ; Xiao, Xiaodong ; Camara, Maria M. ; DiGiandomenico, Antonio ; Semenova, Elena ; Lanzavecchia, Antonio ; Warrener, Paul ; Suzich, JoAnn ; Wang, Qun ; Corti, Davide ; Stover, C. Kendall

In: Nature communications, 2017, vol. 8, p. 1991

Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all...

Università della Svizzera italiana

Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

Lindesmith, Lisa C. ; Mallory, Michael L. ; Debbink, Kari ; Donaldson, Eric F. ; Brewer-Jensen, Paul D. ; Swann, Excel W. ; Sheahan, Timothy P. ; Graham, Rachel L. ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: mSphere, 2018, vol. 3, no. 1, p. e00518-17

Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross- protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by...

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

Identification of a novel non-desmoglein autoantigen in Pemphigus Vulgaris

Di Lullo, Giulia ; Calabresi, Valentina ; Mariotti, Feliciana ; Zambruno, Giovanna ; Lanzavecchia, Antonio ; Di Zenzo, Giovanni

In: Frontiers in immunology, 2019, vol. 10, p. 1391

Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied...

Università della Svizzera italiana

Protection of calves by a prefusion-stabilized bovine RSV F vaccine

Zhang, Baoshan ; Chen, Lei ; Silacci, Chiara ; Thom, Michelle ; Boyington, Jeffrey C. ; Druz, Aliaksandr ; Joyce, M. Gordon ; Guzman, Efrain ; Kong, Wing-Pui ; Lai, Yen-Ting ; Stewart-Jones, Guillaume B. E. ; Tsybovsky, Yaroslav ; Yang, Yongping ; Zhou, Tongqing ; Baxa, Ulrich ; Mascola, John R. ; Corti, Davide ; Lanzavecchia, Antonio ; Taylor, Geraldine ; Kwong, Peter D.

In: Npj vaccines, 2017, vol. 2, p. 7

Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated...

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

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...