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

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

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

Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41

Sabin, Charles ; Corti, Davide ; Buzon, Victor ; Seaman, Mike S. ; Hulsik, David Lutje ; Hinz, Andreas ; Vanzetta, Fabrizia ; Agatic, Gloria ; Silacci, Chiara ; Mainetti, Lara ; Scarlatti, Gabriella ; Sallusto, Federica ; Weiss, Robin ; Lanzavecchia, Antonio ; Weissenhorn, Winfried

In: Plos pathogens, 2010, vol. 6, no. 11, p. e1001195

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 A° resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a...

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...