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Università della Svizzera italiana

Antibody-guided vaccine design : identification of protective epitopes

Lanzavecchia, Antonio ; Frühwirth, Alexander ; Perez, Laurent ; Corti, Davide

In: Current opinion in immunology, 2016, vol. 41, no. August, p. 62-67

In the last decade, progress in the analysis of the human immune response and in the isolation of human monoclonal antibodies have provided an innovative approach to the identification of protective antigens which are the basis for the design of vaccines capable of eliciting effective B-cell immunity. In this review we illustrate, with relevant examples, the power of this approach that can...

Université de Fribourg

β-Arrestin1 and β-Arrestin2 are required to support the activity of the CXCL12/HMGB1 heterocomplex on CXCR4

D’Agostino, Gianluca ; Artinger, Marc ; Locati, Massimo ; Perez, Laurent ; Legler, Daniel F. ; Bianchi, Marco E. ; Rüegg, Curzio ; Thelen, Marcus ; Marchese, Adriano ; Rocchi, Marco B. L. ; Cecchinato, Valentina ; Uguccioni, Mariagrazia

In: Frontiers in Immunology, 2020, vol. 11, p. -

The chemokine receptor CXCR4 plays a fundamental role in homeostasis and pathology by orchestrating recruitment and positioning of immune cells, under the guidance of a CXCL12 gradient. The ability of chemokines to form heterocomplexes, enhancing their function, represents an additional level of regulation on their cognate receptors. In particular, the multi-faceted activity of the...

Università della Svizzera italiana

Virus-like particles and nanoparticles for vaccine development against HCMV

Perotti, Michela ; Perez, Laurent

In: Viruses, 2020, vol. 12, no. 1, p. 17 p

Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection still represents an unmet clinical need and a life-threatening disease in...

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

HCMV envelope glycoprotein diversity demystified

Foglierini, Mathilde ; Marcandalli, Jessica ; Perez, Laurent

In: Frontiers in microbiology, 2019, vol. 10, p. 1005

Human cytomegalovirus (HCMV) is the leading viral cause of congenital birth defects and is responsible for morbidity and mortality in immunosuppressed individuals. Considerable efforts have been deployed over the last decade to develop a vaccine capable of preventing HCMV infection. However, in recent clinical trials, vaccines showed at best modest efficacy in preventing infection. These...

Università della Svizzera italiana

The C-terminal domain of TPX2 is made of alpha-helical tandem repeats

Sanchez-Pulido, Luis ; Perez, Laurent ; Kuhn, Steffen ; Vernos, Isabelle ; Andrade-Navarro, Miguel A.

In: BMC structural biology, 2016, vol. 16, p. 17

Background: TPX2 (Targeting Protein for Xklp2) is essential for spindle assembly, activation of the mitotic kinase Aurora A and for triggering microtubule nucleation. Homologs of TPX2 in Chordata and plants were previously identified. Currently, proteins of the TPX2 family have little structural information and only small parts are covered by defined protein domains. Methods: We have used ...

Università della Svizzera italiana

Hitting the right spot : mechanism of action of OPB‐31121, a novel and potent inhibitor of the Signal Transducer and Activator of Transcription 3 (STAT3)

Brambilla, Lara ; Genini, Davide ; Laurini, Erik ; Merulla, Jessica ; Perez, Laurent ; Fermeglia, Maurizio ; Carbone, Giuseppina M. ; Pricl, Sabrina ; Catapano, Carlo V.

In: Molecular oncology, 2015, vol. 9, no. 6, p. 1194-1206

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB‐31121, an anticancer compound currently in clinical trials, has been reported to affect...

Università della Svizzera italiana

Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies

Kabanovaa, Anna ; Perez, Laurent ; Lilleri, Daniele ; Marcandalli, Jessica ; Agatic, Gloria ; Becattini, Simone ; Preite, Silvia ; Fuschillo, Dario ; Percivalle,Elena ; Sallusto, Federica ; Gerna, Giuseppe ; Corti, Davide ; Lanzavecchia, Antonio

In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970

The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...