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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

Identification and structure of a multidonor class of head-directed influenza-neutralizing antibodies reveal the mechanism for its recurrent elicitation

Sao-Fong Cheung, Crystal ; Fruehwirth, Alexander ; Paparoditis, Philipp Carl Georg ; Shen, Chen-Hsiang ; Foglierini, Mathilde ; Joyce, M. Gordon ; Leung, Kwanyee ; Piccoli, Luca ; Rawi, Reda ; Silacci-Fregni, Chiara ; Tsybovsky, Yaroslav ; Verardi, Raffaello ; Wang, Lingshu ; Wang, Shuishu ; Yang, Eun Sung ; Zhang, Baoshan ; Zhang, Yi ; Chuang, Gwo-Yu ; Corti, Davide ; Mascola, John R. ; Shapiro, Lawrence ; Kwong, Peter D. ; Lanzavecchia, Antonio ; Zhou, Tongqing

In: Cell reports, 2020, vol. 32, no. 9, p. 12 p

Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class...

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...

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

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)...