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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

Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

Hu, Dan ; Notarbartolo, Samuele ; Croonenborghs, Tom ; Patel, Bonny ; Cialic, Ron ; Yang, Tun-Hsiang ; Aschenbrenner, Dominik ; Andersson, Karin M. ; Gattorno, Marco ; Pham, Minh ; Kivisakk, Pia ; Pierre, Isabelle V. ; Lee, Youjin ; Kiani, Karun ; Bokarewa, Maria ; Tjon, Emily ; Pochet, Nathalie ; Sallusto, Federica ; Kuchroo, Vijay K. ; Weiner, Howard L.

In: Nature communications, 2017, vol. 8, p. 1600

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene...

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

TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut

Romagnani, Andrea ; Vettore, Valentina ; Rezzonico-Jost, Tanja ; Hampe, Sarah ; Rottoli, Elsa ; Nadolni, Wiebke ; Perotti, Michela ; Meier, Melanie A. ; Hermanns, Constanze ; Geiger, Sheila ; Wennemuth, Gunther ; Recordati, Camilla ; Matsushita, Masayuki ; Muehlich, Susanne ; Proietti, Michele ; Chubanov, Vladimir ; Gudermann, Thomas ; Grassi, Fabio ; Zierler, Susanna

In: Nature communications, 2017, vol. 8, p. 1917

The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of ...

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

Label-free biosensor detection of endocrine disrupting compounds using engineered estrogen receptors

La Spina, Rita ; Ferrero, Valentina E. V. ; Aiello, Venera ; Pedotti, Mattia ; Varani, Luca ; Lettieri, Teresa ; Calzolai, Luigi ; Haasnoot, Willem ; Colpo, Pascal

In: Biosensors, 2018, vol. 8, no. 1, p. 1-15

Endocrine Disrupting Compounds (EDCs) are chemical substances shown to interfere with endogenous hormones affecting the endocrine, immune and nervous systems of mammals. EDCs are the causative agents of diseases including reproductive disorders and cancers. This highlights the urgency to develop fast and sensitive methods to detect EDCs, which are detrimental even at very low concentrations....

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...