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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

The antibody response to Plasmodium falciparum : cues for vaccine design and the discovery of receptor-based antibodies

Tan, Joshua ; Piccoli, Luca ; Lanzavecchia, Antonio

In: Annual Review of Immunology

P. falciparum remains a serious public health problem and a continuous challenge for the immune system due to the complexity and diversity of the pathogen. Recent advances from several laboratories in the characterization of the antibody response to the parasite have led to the identification of critical targets for protection and revealed a new mechanism of diversification based on the...

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

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...