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Université de Fribourg

In vivo function of the lipid raft protein flotillin-1 during cd8+ t cell–mediated host surveillance

Ficht, Xenia ; Ruef, Nora ; Stolp, Bettina ; Samson, Guerric P. B. ; Moalli, Federica ; Page, Nicolas ; Merkler, Doron ; Nichols, Ben J. ; Diz-Muñoz, Alba ; Legler,, Daniel F. ; Niggli, Verena

In: The Journal of Immunology, 2019, p. -

Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft– associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired because of a decrease in myosin II–mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. In this study, we analyzed morphology and migration...

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...

Université de Fribourg

Biological sex influences antibody responses to routine vaccinations in the first year of life

Zimmermann, Petra ; Perrett, Kirsten P. ; Ritz,  Nicole ; Flanagan, Katie L. ; Robins-Browne, Roy ; Klis, Fiona R. M. van der ; Curtis, Nigel ; the MIS BAIR group

In: Acta Paediatrica, 2019, p. -

Aim We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. Methods One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured...

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

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

Epigenetic and transcriptional control of mast cell responses

Monticelli, Silvia ; Leoni

In: F1000 research, 2017, vol. 6, p. 2064

Mast cells are tissue-resident, innate immune cells present in most tissues of the body and are important effector and immunomodulatory cells. Differentiated mast cells typically are characterized by the surface expression of the receptors KIT and FcεRI, the latter especially being important for stimulation through IgE antibodies, although these cells have the ability to respond to a wide...

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

Dissecting human antibody responses: useful, basic and surprising findings

Lanzavecchia, Antonio

In: EMBO molecular medicine, 2018, vol. 10, p. e8879

Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells...

Università della Svizzera italiana

Epicutaneous allergen application preferentially boosts specific T cell responses in sensitized patients

Campana, Raffaela ; Moritz, Katharina ; Neubauer, Angela ; Huber, Hans ; Henning, Rainer ; Brodie, Tess M. ; Kaider, Alexandra ; Sallusto, Federica ; Wöhrl, Stefan ; Valenta, Rudolf

In: Scientific reports, 2017, vol. 7, p. 11657

The effects of epicutaneous allergen administration on systemic immune responses in allergic and non-allergic individuals has not been investigated with defined allergen molecules. We studied the effects of epicutaneous administration of rBet v 1 and rBet v 1 fragments on systemic immune responses in allergic and non-allergic subjects. We conducted a clinical trial in which rBet v 1 and two...