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Università della Svizzera italiana

Structural basis for broad HIV-1 neutralization by the MPER-specific human broadly neutralizing antibody LN01

Pinto, Dora ; Fenwick, Craig ; Caillat, Christophe ; Silacci, Chiara ; Guseva, Serafima ; Dehez, François ; Chipot, Christophe ; Barbieri, Sonia ; Minola, Andrea ; Jarrossay, David ; Tomaras, Georgia D. ; Shen, Xiaoying ; Riva, Agostino ; Tarkowski, Maciej ; Schwartz, Olivier ; Bruel, Timothée ; Dufloo, Jérémy ; Seaman, Michael S. ; Montefiori, David C. ; Lanzavecchia, Antonio ; Corti, Davide ; Pantaleo, Giuseppe ; Weissenhorn, Winfried

In: Cell host & microbe, 2019, vol. 26, no. 5, p. p. 623-637.e8

Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived...

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

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

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...

Università della Svizzera italiana

Serum immunoglobulin a cross-strain blockade of human noroviruses

Lindesmith, Lisa C. ; Beltramello, Martina ; Swanstrom, Jesica ; Jones, Taylor A. ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Open forum infectious diseases, 2015, vol. 2, no. 3, p. ofv084

Background: Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods: Immunoglobulin (Ig)A was purified...

Università della Svizzera italiana

Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

Piccoli, Luca ; Campo, Ilaria ; Fregni, Chiara Silacci ; Fernandez Rodriguez, Blanca Maria ; Minola, Andrea ; Sallusto, Federica ; Luisetti, Maurizio ; Corti, Davide ; Lanzavecchia, Antonio

In: Nature communications, 2015, vol. 6, p. 7375

Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF...

Università della Svizzera italiana

The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep ; Gach, Johannes S. ; Becerra, Juan C. ; Phan, Tran B. ; Pudney, Jeffrey ; Moldoveanu, Zina ; Joseph, Sarah B. ; Landucci, Gary ; Supnet, Medalyn Jude ; Ping, Li-Hua ; Corti, Davide ; Moldt, Brian ; Hel, Zdenek ; Lanzavecchia, Antonio ; Ruprecht, Ruth M. ; Burton, Dennis R. ; Mestecky, Jiri ; Anderson, Deborah J. ; Forthal, Donald N.

In: Plos pathogens, 2013, vol. 9, no. 11, p. e1003776

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env- specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis...