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5,625 results on '"Bottazzi, A"'

151. Examples and counterexamples regarding hyperfinite representations of real distributions

Author

Emanuele Bottazzi

Subjects
Nonstandard analysis, Generalized functions, Mathematics, QA1-939
Abstract

We provide some examples and counterexamples regarding hyperfinite representations of real distributions. We examine some hyperfinite representatives of the null distribution and of the Dirac distribution, we discuss hyperfinite representations of an infinite Lpnorm, and we study the failure of an energy inequality for the discrete Laplacian in dimension 1. These examples are relevant for the study of partial differential equations with hyperfinite techniques.

Published
2022
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152. The interferon landscape along the respiratory tract impacts the severity of COVID-19

Author

Sposito, Benedetta, Broggi, Achille, Pandolfi, Laura, Crotta, Stefania, Clementi, Nicola, Ferrarese, Roberto, Sisti, Sofia, Criscuolo, Elena, Spreafico, Roberto, Long, Jaclyn M., Ambrosi, Alessandro, Liu, Enju, Frangipane, Vanessa, Saracino, Laura, Bozzini, Sara, Marongiu, Laura, Facchini, Fabio A., Bottazzi, Andrea, Fossali, Tommaso, Colombo, Riccardo, Clementi, Massimo, Tagliabue, Elena, Chou, Janet, Pontiroli, Antonio E., Meloni, Federica, Wack, Andreas, Mancini, Nicasio, and Zanoni, Ivan

Published
2021
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153. Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic

Author

Hotez, Peter J., Batista, Carolina, Amor, Yanis Ben, Ergonul, Onder, Figueroa, J Peter, Gilbert, Sarah, Gursel, Mayda, Hassanain, Mazen, Kang, Gagandeep, Kaslow, David C., Kim, Jerome H., Lall, Bhavna, Larson, Heidi, Naniche, Denise, Sheahan, Timothy, Shoham, Shmuel, Wilder-Smith, Annelies, Sow, Samba O., Strub-Wourgaft, Nathalie, Yadav, Prashant, and Bottazzi, Maria Elena

Published
2021
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155. A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2

Author

Syamala Rani Thimmiraju, Rakesh Adhikari, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Rakhi Kundu, Yi-Lin Chen, Suman Sharma, Karm Ghei, Brian Keegan, Leroy Versteeg, Portia M. Gillespie, Allan Ciciriello, Nelufa Y. Islam, Cristina Poveda, Nestor Uzcategui, Wen-Hsiang Chen, Jason T. Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J. Hotez, and Jeroen Pollet

Subjects
immune escape, vaccine efficacy, COVID-19, SARS-CoV-2, Medicine
Abstract

(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia, it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5, and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, the serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of the high antibody cross-reactivity with ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants with the sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, the sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.

Published
2023
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156. Combined use of LS-PIV and CFD for the characterization of turbulent flow in the contact chamber of ‘COSTA AZUL’ wastewater treatment plant, Carlos Paz

Author

Ragessi I. Matias, Leyria Rainieri Gianina, Ganancias Facundo, García C. Marcelo, Di Buo Melina, and Balangero Bottazzi Gerardo

Subjects
cfd, contact chamber, ls-piv, turbulent flow, wwtp, Information technology, T58.5-58.64, Environmental technology. Sanitary engineering, TD1-1066
Abstract

The Costa Azul wastewater treatment plant is situated in Carlos Paz city (Córdoba, Argentina). The treated water is discharged to the San Roque reservoir, which is the source of water for the city of Córdoba and surrounding towns. Consequently, it is of great importance to evaluate the potential impact on the water quality reservoir for the preservation of public health. Currently, the WWTP lacks an accurate flow monitoring system at the last treatment: disinfection. This problem led to the development of a methodology in which experimental in-situ work and computational fluid dynamics (CFD) were applied, in a combined way, to calibrate the flow measurement system. First, large-scale particle image velocimetry (LS-PIV) was applied. The results made it possible to obtain characteristic parameters of the average flow: cross-sectional velocity profiles, recirculation and flow stagnation zones, flow discharge and characteristic parameters of the contact chamber. Second, numerical models, based on the Reynolds-average Navier–Stokes equations with the k–ε turbulent closure model were used. Based on the simulation results, it was possible to calibrate the discharge equation for a rectangular weir, and elaborate recommendations to improve the discharge measurement system and hydraulics in the area of the contact chamber curves. HIGHLIGHTS CFD simulation was used to build a head-flow curve and obtain a detail characterization of flow hydrodynamics.; Five design alternatives were modeled to improve the flow hydraulics in order to achieve the most uniform possible distribution of residence time.; Large-scale particle image velocimetry (LS-PIV) was applied to characterize of turbulent flow in prototype scale contact chamber.;

Published
2021
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157. Identification of vaccine targets in pathogens and design of a vaccine using computational approaches

Author

Kamal Rawal, Robin Sinha, Bilal Ahmed Abbasi, Amit Chaudhary, Swarsat Kaushik Nath, Priya Kumari, P. Preeti, Devansh Saraf, Shachee Singh, Kartik Mishra, Pranjay Gupta, Astha Mishra, Trapti Sharma, Srijanee Gupta, Prashant Singh, Shriya Sood, Preeti Subramani, Aman Kumar Dubey, Ulrich Strych, Peter J. Hotez, and Maria Elena Bottazzi

Subjects
Medicine, Science
Abstract

Abstract Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (

Published
2021
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158. SARS‑CoV-2 RBD219-N1C1: A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice

Author

Jeroen Pollet, Wen-Hsiang Chen, Leroy Versteeg, Brian Keegan, Bin Zhan, Junfei Wei, Zhuyun Liu, Jungsoon Lee, Rahki Kundu, Rakesh Adhikari, Cristina Poveda, Maria Jose Villar, Ana Carolina de Araujo Leao, Joanne Altieri Rivera, Zoha Momin, Portia M. Gillespie, Jason T. Kimata, Ulrich Strych, Peter J. Hotez, and Maria Elena Bottazzi

Subjects
covid-19, rbd, alum, pseudovirus, coronavirus, ace-2, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here, we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1,000 to 1:10,000 range, for both antigens tested. The vaccines induced IFN-γ IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel® containing formulation and possibly in combination with other immunostimulants.

Published
2021
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159. Operation Warp Speed: implications for global vaccine security

Author

Kim, Jerome H, Hotez, Peter, Batista, Carolina, Ergonul, Onder, Figueroa, J Peter, Gilbert, Sarah, Gursel, Mayda, Hassanain, Mazen, Kang, Gagandeep, Lall, Bhavna, Larson, Heidi, Naniche, Denise, Sheahan, Timothy, Shoham, Shmuel, Wilder-Smith, Annelies, Strub-Wourgaft, Nathalie, Yadav, Prashant, and Bottazzi, Maria Elena

Published
2021
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161. Genetic modification to design a stable yeast-expressed recombinant SARS-CoV-2 receptor binding domain as a COVID-19 vaccine candidate

Author

Chen, Wen-Hsiang, Wei, Junfei, Kundu, Rakhi Tyagi, Adhikari, Rakesh, Liu, Zhuyun, Lee, Jungsoon, Versteeg, Leroy, Poveda, Cristina, Keegan, Brian, Villar, Maria Jose, de Araujo Leao, Ana C., Rivera, Joanne Altieri, Gillespie, Portia M., Pollet, Jeroen, Strych, Ulrich, Zhan, Bin, Hotez, Peter J., and Bottazzi, Maria Elena

Published
2021
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162. Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Author

Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johanes, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Veyckemans, Francis, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Joris, Butković, Diana, Sorić, Ivana Kerovec, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, Rene, Cajkova, Petra, Mixa, Vladimir, Sedlačkova, Yvona, Knoppova, Lenka, Zlamalova (nee Květoňova), Alena, Vavřina, Martin, Žurek, Jiři, Hansen, Tom, Afshari, Arash, Bille, Anders B., Ellekvist, Marguerite, Ilmoja, Mari-Liis, Moor, Reet, Kikas, Reet, Vali, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vahatalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugues, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Herve, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Gaulain, Karine Nouette, Hamonic, Yann, Semjen, Francois, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cecile, Petry, Lea, Ros, Lilica, Zang, Aurelien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thomas, Fabre, Fanny, Legrand, Aurelien, Druot, Emilie, Orliaguet, Gilles, Sabau, Lucie, Uhrig, Lynn, de la Briere, Francois, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Kaufmann, Jost, Laschat, Michael, Wappler, Frank, Becke, Karin, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thomas, Diers, Anja, Schorer, Clemens, Weyland, Andreas, Cohausz, Ruth, Kretz, Franz-Josef, Loffler, Michaela, Wilbs, Markus, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthias, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thomas, Richter, Daniel, Schafer, Melanie, Weigand, Markus, Weiterer, Sebastian, Ochsenreiter, Miriam, Scholer, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicolas, Menzel, Christoph, Trieschmann, Uwe, Yucetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Sohle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemis, Tsiotou, Adelais, Sapi, Erzsebet, Szekely, Edgar, Kosik, Nandor, Maraczi, Veronika, Schnur, Janos, Csillag, Judit, Gal, Janos, Gobl, Gergely, Hauser, Balazs, Petroczy, Andras, Tovishazi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria C., Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura B., Finamore, Simona A., Porro, Giuliana A., Bonfiglio, Rachele, Disma, Nicola, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald R., Favarato, Moreno, Locatelli, Bruno G., Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rients, Emal, Dina, Stevens, Markus, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andreas, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der, Anouk, Dortmont, Knijff-van, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella M., Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Bas, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger M., Isern, Erik R., Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Zielinska, Marzena, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Silvia, Patuleia, Maria Domingas, Esteves, Catarina C., Salgado, Helena, Santos, Maria J., Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyiri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Racic, Selena Puric, Simic, Dusica, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanova, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Štupnik, Špela P., Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandstrom, Kerstin, Bengt, Sporre, Dorenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnstrom, Ann, Ponten, Emma, Bruelisauer, Thomas, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathias, Riva, Thomas, Seiler, Stefan, Bogli, Yann, Dolci, Mirko, Marcucci, Carine, Habre, Walid, Pichon, Isabelle, Vutskits, Laszlo, Casutt, Mattias, Holzle, Martin, Hurni, Thomas, Johr, Martin, Anna-Ursina, Malar, Mauch, Jacqueline, Erb, Thomas, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse C., Hatipoğlu, Zehra, Ozcengiz, Dilek, Erdost, Hale Aksu, Ocmen, Elvan, Olguner, Cimen, Ayanoglu, Hilmi, Dincer, Pelin C., Umuroglu, Tumay, Azizoglu, Mustafa, Birbicer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargis, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Barry, Juliet W., Abbott, Joy, Armstrong, James, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Catenacci, Stefano S., Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chris, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, Virag, Katalin, Hansen, Tom G., Harlet, Pierre, Walker, Suellen M., de Graaff, Jurgen C., and Engelhardt, Thomas

Published
2021
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163. Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

Author

Breschan, Christian, Likar, Rudolf, Platzer, Manuela, Edelman, Isole, Eger, Johanes, Heschl, Stefan, Messerer, Brigitte, Vittinghof, Maria, Kroess, Ruth, Stichlberger, Martina, Kahn, David, Pirotte, Thierry, Pregardien, Caroline, Veyckemans, Francis, Stevens, France, Berghmans, Johan, Bauters, Annemie, De Baerdemaeker, Luc, De Hert, Stefan, Lapage, Koen, Parashchanka, Aliaksandra, Van Limmen, Jurgen, Wyffels, Piet, Lauweryns, Julie, Najafi, Nadia, Vundelinckx, Joris, Butković, Diana, Kerovec Sorić, Ivana, Kralik, Sandra, Markić, Ana, Azman, Josip, Markic, Josko, Pupacic, Daniela, Frelich, Michal, Reimer, Petr, Urbanec, René, Cajková, Petra, Mixa, Vladimír, Sedláčková, Yvona, Knoppová, Lenka, Zlámalová (neé Květoňová), Alena, Vavřina, Martin, Žurek, Jiří, Hansen, Tom, Afshari, Arash, Bille, Anders Bastholm, Ellekvist, Marguerite, Ilmoja, Mari-Liis, Moor, Reet, Kikas, Reet, Väli, Merle, Kallio, Kariantti, Reponen, Elisa, Suominen, Pertti, Suvanto, Sami, Vähätalo, Raisa, Kokki, Hannu, Kokki, Merja, Harju, Jarkko, Kokkonen, Miia, Vieri, Jenni, Manner, Tuula, Amory, Catherine, Ludot, Hugues, Bert, Dina, Godart, Juliette, Laffargue, Anne, Dupont, Hervé, Urbina, Benjamin, Baujard, Catherine, Roulleau, Philippe, Staiti, Giuseppe, Bordes, Maryline, Nouette Gaulain, Karine, Hamonic, Yann, Semjen, François, Jacqmarcq, Olivier, Lejus-Bourdeau, Caroline, Magne, Cécile, Petry, Léa, Ros, Lilica, Zang, Aurélien, Bennis, Mehdi, Coustets, Bernard, Fesseau, Rose, Constant, Isabelle, Khalil, Eliane, Sabourdin, Nada, Audren, Noemie, Descarpentries, Thomas, Fabre, Fanny, Legrand, Aurélien, Druot, Emilie, Orliaguet, Gilles, Sabau, Lucie, Uhrig, Lynn, de la Brière, François, Jonckheer, Karin, Mission, Jean-Paul, Scordo, Lucia, Couchepin, Caroline, Dadure, Christophe, De la Arena, Pablo, Hertz, Laurent, Pirat, Philippe, Sola, Chrystelle, Bellon, Myriam, Dahmani, Souhayl, Julien-Marsollier, Florence, Michelet, Daphne, Depret-Donatien, Veronique, Lesage, Anne, Kaufmann, Jost, Laschat, Michael, Wappler, Frank, Becke, Karin, Brunner, Lena, Oppenrieder, Karin, Badelt, Gregor, Hochmuth, Karin, Koller, Bernhard, Reil, Anita, Richter, Sebastian, Fischer, Thomas, Diers, Anja, Schorer, Clemens, Weyland, Andreas, Cohausz, Ruth, Kretz, Franz-Josef, Löffler, Michaela, Wilbs, Markus, Hoehne, Claudia, Ulrici, Johanna, Goeters, Christiane, Flinspach, Armin, Klages, Matthias, Lindau, Simone, Messroghli, Leila, Zacharowski, Kai, Eisner, Christoph, Mueller, Thomas, Richter, Daniel, Schäfer, Melanie, Weigand, Markus, Weiterer, Sebastian, Ochsenreiter, Miriam, Schöler, Michael, Terboven, Tom, Eggemann, Isabel, Haussmann, Sascha, Leister, Nicolas, Menzel, Christoph, Trieschmann, Uwe, Yücetepe, Sirin, Keilig, Susanna, Kranke, Peter, Jelting, Yvonne, Baehner, Torsten, Ellerkmann, Richard, Ghamari, Shahab, Neumann, Claudia, Söhle, Martin, Chloropoulou, Pelagia, Ntritsou, Vagia, Papagiannopoulou, Pinelopi, Garini, Eleana, Karafotia, Afroditi, Mammi, Panagoula, Bali, Evangelia, Iordanidou, Despoina, Malisiova, Anna, Polyzoi, Artemis, Tsiotou, Adelais, Sapi, Erzsebet, Székely, Edgar, Kosik, Nandor, Maráczi, Veronika, Schnur, Janos, Csillag, Judit, Gál, János, Göbl, Gergely, Hauser, Balázs, Petróczy, András, Tövisházi, Gyula, Blain, Stuart, Gallagher, Sarah, Harte, Sinead, Jackson, Mandy, Meehan, Emma, Nawoor, Zeenat, O’Hare, Brendan, Ross, Mark, Lerro, Daniela, Astuto, Marinella, Grasso, Chiara, Scalisi, Rita, Frasacco, Giulia, Lenares, Elena, Leone, Roberto, Grazzini, Maurizia, Minardi, Carmelo, Zadra, Nicola, Cinnella, Gilda, Cotoia, Antonella, Galante, Dario, De Lorenzo, Brita, Kuppers, Beate, Bottazzi, Giulia, Caramelli, Fabio, Mondardini, Maria Cristina, Rossetti, Emanuele, Picardo, Sergio, Vittori, Alessandro, Camporesi, Anna, Wolfler, Andrea, Calderini, Edoardo, Colantonio, Laura Brigitta, Finamore, Simona Anna, Porro, Giuliana Anna, Bonfiglio, Rachele, Disma, Nicola, Kotzeva, Svetlana, Mameli, Leila, Mattioli, Girolamo, Micalizzi, Camilla, Montaguti, Alessia, Pistorio, Angela, Zanaboni, Clelia, Guddo, Anna, Neba, Gerald Rogan, Favarato, Moreno, Locatelli, Bruno Guido, Maffioletti, Micol, Sonzogni, Valter, Garra, Rossella, Sammartino, Maria, Sbaraglia, Fabio, Cortegiani, Andrea, Moscarelli, Alessandra, Attanasi, Elena, Tesoro, Simonetta, Agapiti, Cristina, Pinzoni, Francesca, Vezzoli, Cesare, Bilotta, Federico, Barzdina, Arta, Straume, Zane, Zundane, Anda, Lukosiene, Laura, Maraulaite, Irena, Razlevice, Ilona, Schmitz, Bernd, Mifsud, Stephanie, Aehling, Carolin, Allison, Celia, De Boer, Rients, Emal, Dina, Stevens, Markus, Buitenhuis, Marielle, de Graaff, Jurgen, De Liefde, Inge, Machotta, Andreas, Scoones, Gail, Staals, Lonneke, Tomas, Jeremy, Van der Knijff-van Dortmont, Anouk, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Schafrat, Eva, Schreiber, Jan, Vermeulen, Petronella Mari, Hendriks, Mark, Lako, Sandra, Voet-Lindner, Marieke, Pieters, Barbe, Scheffer, Gert-Jan, Tielens, Luc, Absalom, Anthony R., Bergsma, Margot, De Ruiter, Joke, Meier, Sascha, Volkers, Martin, Zweers, Tjerk, Beukers, Anne M., Boer, Christa, Dertinger, Jurgen, Numan, Sandra, Van Zaane, Bas, Boerke, Wenche B., Ekiz, Nil, Stensrud, Kristoffer, Drage, Inger Marie, Isern, Erik Ramon, Bartkowska-Sniatkowska, Alicja, Grzeskowiak, Malgorzata, Juzwa-Sobieraj, Magdalena, Rosada-Kurasińska, Jowita, Baranowski, Artur, Jakubowska, Karina, Lewandowska, Dorota, Mierzewska-Schmidt, Magdalena, Sawicki, Piotr, Urban-Lechowicz, Magdalena, Przemyslaw, Pomianek, Zielinska, Marzena, Leal, Teresa, Soares, Maria, Pina, Pedro, Pinho, Sílvia, Patuleia, Maria Domingas, Esteves, Catarina Cruz, Salgado, Helena, Santos, Maria João, Badeti, Rodica, Cindea, Iulia, Oana, Loredana, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Tabacaru, Radu, Trante, Irina, Munteanu, Valentin, Morariu, Mihai, Nyíri, Emese, Budic, Ivana, Marjanovic, Vesna, Drašković, Biljana, Pandurov, Marina, Ilic, Jordanka, Mandras, Ana, Rados, Zdenka, Stankovic, Nikola, Suica, Maja, Vasiljevic, Sladjana, Knezevic, Mirjana, Milojevic, Irina, Petrov, Ivana, Puric Racic, Selena, Simic, Dusica, Simic, Irena, Stevic, Marija, Vulicevic, Irena, Cabanová, Barbora, Hanula, Miloslav, Berger, Jelena, Janjatovic, Darja, Pirtovšek Štupnik, Špela, Méndez, Dolores, Pino, Gema, Rubio, Paloma, Izquierdo, Alberto, López, Silvia, González Serrano, Cristina, Cebrián, Jesús, Peleteiro, Ana, Del Rey de Diego, Pilar, Martínez García, Ernesto, Tormo de las Heras, Carolina, Troncoso Montero, Pablo, Arbona, Celia, Artés, David, Chamizo, Alicia, Serrano, Silvia, Suarez Comas, Montserrat, Escribá, Francisco, Auli, Cristina, Pérez Pardo, Osvaldo, Sierra Biddle, Natalia, Suárez Castaño, Ceferina, Villalobos Rico, María Isabel, Manrique Muñoz, Susana, García Martínez, Irene, Montferrer Estruch, Nuria, Vilardell Ortíz, Elena, Poves-Álvarez, Rodrigo, Kohn, Ivan, Lindestam, Ulf, Reinhard, Jarl, Castellheim, Albert, Sandström, Kerstin, Bengt, Sporre, Dörenberg, Rainer, Frykholm, Peter, Garcia, Maria, Kvarnström, Ann, Pontén, Emma, Bruelisauer, Thomas, Erdoes, Gabor, Kaiser, Heiko, Marchon, Mathias, Riva, Thomas, Seiler, Stefan, Bögli, Yann, Dolci, Mirko, Marcucci, Carine, Habre, Walid, Pichon, Isabelle, Vutskits, Laszlo, Casutt, Mattias, Hölzle, Martin, Hurni, Thomas, Jöhr, Martin, Malär, Anna-Ursina, Mauch, Jacqueline, Erb, Thomas, Oeinck, Karin, Akin, Mine, Keskin, Gulsen, Senayli, Yesim, Kaya, Guner, Kendigelen, Pinar, Tutuncu, Ayse Çiğdem, Hatipoğlu, Zehra, Özcengiz, Dilek, Erdost, Hale Aksu, Öçmen, Elvan, Olguner, Çimen, Ayanoglu, Hilmi, Dincer, Pelin Corman, Umuroglu, Tumay, Azizoglu, Mustafa, Birbiçer, Handan, Doruk, Nurcan, Sagun, Aslı, Baris, Sibel, Dmytriiev, Dmytro, Kuchi, Sridevi, Masip, Nuria, Brooks, Peter, Hare, Alison, Ahmad, Nargis, Casey, Michelle, De Silva, Sam, Dobby, Nadine, Krishnan, Prakash, Sogbodjor, L. Amaki, Walker, Ellie, Walker, Suellen, King, Stephanie, Nicholson, Katy, Quinney, Michelle, Stevens, Paul, Blevin, Andrew, Giombini, Mariangela, Goonasekera, Chulananda, Adil, Sadia, Bew, Stephanie, Bodlani, Carol, Gilpin, Dan, Jinks, Stephanie, Malarkkan, Nalini, Miskovic, Alice, Pad, Rebecca, Wolfe Barry, Juliet, Abbott, Joy, Armstrong, James, Cooper, Natalie, Crate, Lindsay, Emery, John, James, Kathryn, King, Hannah, Martin, Paul, Scalia Catenacci, Stefano, Bomont, Rob, Smith, Paul, Mele, Sara, Verzelloni, Alessandra, Dix, Philippa, Bell, Graham, Gordeva, Elena, McKee, Lesley, Ngan, Esther, Scheffczik, Jutta, Tan, Li-En, Worrall, Mark, Cassar, Carmel, Goddard, Kevin, Barlow, Victoria, Oshan, Vimmi, Shah, Khairi, Bell, Sarah, Daniels, Lisa, Gandhi, Monica, Pachter, David, Perry, Chris, Robertson, Andrew, Scott, Carmen, Waring, Lynne, Barnes, David, Childs, Sophie, Norman, Joanne, Sunderland, Robin, Julia, Dowell, Prisca, Feijten, Pierre, Harlet, Sarah, Herbineaux, Brigitte, Leva, Benoît, Plichon, Katalin, Virág, Virag, Katalin, and Engelhardt, Thomas

Published
2021
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168. Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19

Author

Gritti, Giuseppe, Raimondi, Federico, Bottazzi, Barbara, Ripamonti, Diego, Riva, Ivano, Landi, Francesco, Alborghetti, Leonardo, Frigeni, Marco, Damiani, Marianna, Micò, Caterina, Fagiuoli, Stefano, Lorini, Ferdinando Luca, Gandini, Lucia, Novelli, Luca, Morgan, Jonathan P., Owens, Benjamin M. J., Kanhai, Karan J. K., Reljanovic, Gordana Tonkovic, Rizzi, Marco, Di Marco, Fabiano, Mantovani, Alberto, and Rambaldi, Alessandro

Published
2021
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170. Safety and immunogenicity of co-administered hookworm vaccine candidates Na-GST-1 and Na-APR-1 in Gabonese adults: a randomised, controlled, double-blind, phase 1 dose-escalation trial

Author

Mouwenda, Yoanne D, Betouke Ongwe, Eunice, Nkoma Mouima, Anne-Marie, Nouatin, Odilon P, Edoa, Jean R, Manouana, Prince G, Pinto de Jesus, Susana, Kühne, Vera, Mordmueller, Benjamin, Lell, Bertrand, Agnandji, Selidji T, Koehler, Carsten, Adegnika, Ayola A, de Vries, Sophia G, Zinsou, Frejus J, Honkepehedji, Yabo J, Dejon Agobé, Jean-Claude, Vodonou, Kafui G, Bikangui, Rodrigue, Bouyoukou Hounkpatin, Aurore, Bache, Emmanuel B, Massinga Loembe, Marguerite, van Leeuwen, Remko, Molemans, Marjan, Kremsner, Peter G, Yazdanbakhsh, Maria, Hotez, Peter J, Bottazzi, Maria Elena, Li, Guangzhao, Bethony, Jeffrey M, Diemert, David J, and Grobusch, Martin P

Published
2021
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171. Long pentraxin 3 (PTX3) levels predict death, intubation and thrombotic events among hospitalized patients with COVID-19

Author

Giuseppe Lapadula, Roberto Leone, Davide Paolo Bernasconi, Andrea Biondi, Emanuela Rossi, Mariella D’Angiò, Barbara Bottazzi, Laura Rachele Bettini, Ilaria Beretta, Cecilia Garlanda, Maria Grazia Valsecchi, Alberto Mantovani, and Paolo Bonfanti

Subjects
COVID - 19, pentraxin 3 (PTX3), mortality, SARS – CoV – 2, inflammation, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundPTX3 is an important mediator of inflammation and innate immunity. We aimed at assessing its prognostic value in a large cohort of patients hospitalized with COVID-19.MethodsLevels of PTX3 were measured in 152 patients hospitalized with COVID-19 at San Gerardo Hospital (Monza, Italy) since March 2020. Cox regression was used to identify predictors of time from admission to in-hospital death or mechanical ventilation. Crude incidences of death were compared between patients with PTX3 levels higher or lower than the best cut-off estimated with the Maximally Selected Rank Statistics Method.ResultsUpon admission, 22% of the patients required no oxygen, 46% low-flow oxygen, 30% high-flow nasal cannula or CPAP-helmet and 3% MV. Median level of PTX3 was 21.7 (IQR: 13.5-58.23) ng/ml. In-hospital mortality was 25% (38 deaths); 13 patients (8.6%) underwent MV. PTX3 was associated with risk of death (per 10 ng/ml, HR 1.08; 95%CI 1.04-1.11; P

Published
2022
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172. A cytokine/PTX3 prognostic index as a predictor of mortality in sepsis

Author

Sadaf Davoudian, Daniele Piovani, Antonio Desai, Sarah N. Mapelli, Roberto Leone, Marina Sironi, Sonia Valentino, Rita Silva-Gomes, Matteo Stravalaci, Fatemeh Asgari, Alessandra Madera, Daniele Piccinini, Carlo Fedeli, Denise Comina, Stefanos Bonovas, Antonio Voza, Alberto Mantovani, and Barbara Bottazzi

Subjects
sepsis, biomarkers, cytokines, PTX3, disease severity, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundEarly prognostic stratification of patients with sepsis is a difficult clinical challenge. Aim of this study was to evaluate novel molecules in association with clinical parameters as predictors of 90-days mortality in patients admitted with sepsis at Humanitas Research Hospital.MethodsPlasma samples were collected from 178 patients, diagnosed based on Sepsis-3 criteria, at admission to the Emergency Department and after 5 days of hospitalization. Levels of pentraxin 3 (PTX3), soluble IL-1 type 2 receptor (sIL-1R2), and of a panel of pro- and anti-inflammatory cytokines were measured by ELISA. Cox proportional-hazard models were used to evaluate predictors of 90-days mortality.ResultsCirculating levels of PTX3, sIL-1R2, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-1ra, TNF-α increased significantly in sepsis patients on admission, with the highest levels measured in shock patients, and correlated with SOFA score (PTX3: r=0.44, p

Published
2022
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173. Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.

Author

Victor Manuel Dzul-Huchim, Maria Jesus Ramirez-Sierra, Pedro Pablo Martinez-Vega, Miguel Enrique Rosado-Vallado, Victor Ermilo Arana-Argaez, Jaime Ortega-Lopez, Fabian Gusovsky, Eric Dumonteil, Julio Vladimir Cruz-Chan, Peter Hotez, María Elena Bottazzi, and Liliana Estefania Villanueva-Lizama

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

BackgroundChagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy used for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and dogs, we propose that immunization with the corresponding recombinant proteins offers an alternative and feasible strategy to develop these antigens as a bivalent human vaccine. We hypothesized that a low dose of BNZ in combination with a therapeutic vaccine (TSA-1-C4 and Tc24-C4 antigens formulated with a synthetic TLR-4 agonist-adjuvant, E6020-SE) given during early chronic infection, could prevent cardiac disease progression and provide antigen-specific T cell immunity.Methodology/ principal findingsWe evaluated the therapeutic vaccine candidate plus BNZ (25 mg/kg/day/7 days) given on days 72 and 79 post-infection (p.i) (early chronic phase). Fibrosis, inflammation, and parasite burden were quantified in heart tissue at day 200 p.i. (late chronic phase). Further, spleen cells were collected to evaluate antigen-specific CD4+ and CD8+ T cell immune response, using flow cytometry. We found that vaccine-linked BNZ treated mice had lower cardiac fibrosis compared to the infected untreated control group. Moreover, cells from mice that received the immunotherapy had higher stimulation index of antigen-specific CD8+Perforin+ T cells as well as antigen-specific central memory T cells compared to the infected untreated control.ConclusionsOur results suggest that the bivalent immunotherapy together with BNZ treatment given during early chronic infection protects BALB/c mice against cardiac fibrosis progression and activates a strong CD8+ T cell response by in vitro restimulation, evidencing the induction of a long-lasting T. cruzi-immunity.

Published
2022
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174. Minimal length curves in unitary orbits of a Hermitian compact operator

Author

Bottazzi, Tamara and Varela, Alejandro

Subjects
Mathematics - Functional Analysis, Mathematics - Operator Algebras, 22F30, 43A85, 47B15, 47A58, 53C22
Abstract

We study some examples of minimal length curves in homogeneous spaces of B(H) under a left action of a unitary group. Recent results relate these curves with the existence of minimal (with respect to a quotient norm) anti-Hermitian operators Z in the tangent space of the starting point. We show minimal curves that are not of this type but nevertheless can be approximated uniformly by those.

Published
2015

175. Serum amyloid P component is an essential element of resistance against Aspergillus fumigatus

Author

Andrea Doni, Raffaella Parente, Ilaria Laface, Elena Magrini, Cristina Cunha, Federico Simone Colombo, João F. Lacerda, António Campos, Sarah N. Mapelli, Francesca Petroni, Rémi Porte, Tilo Schorn, Antonio Inforzato, Toine Mercier, Katrien Lagrou, Johan Maertens, John D. Lambris, Barbara Bottazzi, Cecilia Garlanda, Marina Botto, Agostinho Carvalho, and Alberto Mantovani

Subjects
Science
Abstract

Serum Amyloid P is a humoral component with established roles in the response to bacterial infection and regulation of tissue remodeling. Here the authors provide evidence to a further crucial role of serum amyloid P in the context of fungal pathogen Aspergillus fumigatus.

Published
2021
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177. Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

Author

Maseri, A., Andreini, D., Berti, S., Canestrari, M., Casolo, G., Gabrielli, D., Latini, R., Magnoni, M., Marraccini, P., Masson, S., Moccetti, T., Modena, M.G., Pontone, G., Gaspari, F., Ferrari, S., Cannata, A., Stucchi, N., Fois, M., Bernasconi, R., Balconi, G., Vago, T., Letizia, T., Bottazzi, B., Leone, R., Suliman, I., Sommaruga, M., Gremigni, P., Olivieri, R., Pennacchietti, L., Magnacca, M., Rossi, M.G., Pasotti, E., Clemente, A., Mushtaq, S., Mauro, E., Rossi, R., Pigazzani, F., Faggioni, L., Ciardetti, M., Puppato, M., Conte, Edoardo, Andreini, Daniele, Magnoni, Marco, Masson, Serge, Mushtaq, Saima, Berti, Sergio, Canestrari, Mauro, Casolo, Giancarlo, Gabrielli, Domenico, Latini, Roberto, Marraccini, Paolo, Moccetti, Tiziano, Modena, Maria Grazia, Pontone, Gianluca, Gorini, Marco, Maggioni, Aldo P., and Maseri, Attilio

Published
2021
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180. A process-based approach to understanding and managing triggered seismicity

Author

Hager, Bradford H., Dieterich, James, Frohlich, Cliff, Juanes, Ruben, Mantica, Stefano, Shaw, John H., and Bottazzi, Francesca

Subjects
Seismic prospecting -- Methods, Earthquakes -- Models -- Causes of, Oil and gas exploration -- Environmental aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

There is growing concern about seismicity triggered by human activities, whereby small increases in stress bring tectonically loaded faults to failure. Examples of such activities include mining, impoundment of water, stimulation of geothermal fields, extraction of hydrocarbons and water, and the injection of water, CO.sub.2 and methane into subsurface reservoirs.sup.1. In the absence of sufficient information to understand and control the processes that trigger earthquakes, authorities have set up empirical regulatory monitoring-based frameworks with varying degrees of success.sup.2,3. Field experiments in the early 1970s at the Rangely, Colorado (USA) oil field.sup.4 suggested that seismicity might be turned on or off by cycling subsurface fluid pressure above or below a threshold. Here we report the development, testing and implementation of a multidisciplinary methodology for managing triggered seismicity using comprehensive and detailed information about the subsurface to calibrate geomechanical and earthquake source physics models. We then validate these models by comparing their predictions to subsequent observations made after calibration. We use our approach in the Val d'Agri oil field in seismically active southern Italy, demonstrating the successful management of triggered seismicity using a process-based method applied to a producing hydrocarbon field. Applying our approach elsewhere could help to manage and mitigate triggered seismicity. A multidisciplinary method for managing triggered seismicity is developed using detailed subsurface information to calibrate geomechanical and earthquake source physics models, and is applied to the Val d'Agri oil field in seismically active southern Italy., Author(s): Bradford H. Hager [sup.1] , James Dieterich [sup.2] , Cliff Frohlich [sup.3] , Ruben Juanes [sup.4] [sup.5] , Stefano Mantica [sup.6] , John H. Shaw [sup.7] , Francesca Bottazzi [...]

Published
2021
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182. Adjuvanted Fusion Protein Vaccine Induces Durable Immunity to Onchocerca volvulus in Mice and Non-Human Primates

Author

Nathan M. Ryan, Jessica A. Hess, Erica J. Robertson, Nancy Tricoche, Cheri Turner, Jenn Davis, Nikolai Petrovsky, Melissa Ferguson, William J. Rinaldi, Valerie M. Wong, Ayako Shimada, Bin Zhan, Maria Elena Bottazzi, Benjamin L. Makepeace, Sean A. Gray, Darrick Carter, Sara Lustigman, and David Abraham

Subjects
Onchocerca volvulus, vaccine, durability, adjuvant, mice, non-human primates, Medicine
Abstract

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with Ov-FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that Ov-FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors.

Published
2023
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183. Green Agendas and White Markets: The Coloniality of Agroecology in Senegal

Author

Franziska Marfurt, Tobias Haller, and Patrick Bottazzi

Subjects
agroecology, decolonial political ecologies, alternative food network, migration, climate change, Senegal, Agriculture
Abstract

Development actors in West Africa have been promoting agroecological farming as a solution to combat climate change and to create more sovereign food systems that enhance the autonomy of local smallholders. However, there is a lack of empirical evidence regarding the actual implementation of such programs and their potential to empower smallholders, especially in the West African region. Drawing on co-produced knowledge from anthropological fieldwork in Western Senegal, the case study of an alternative food network explores the interlinkages between the promotion of agroecology, anti-migration policies, and unequal power and market relations. Informed by decolonial political ecologies, the analysis reveals different layers of coloniality which complicate embodied effects on horticultural smallholders. The authors conclude that instead of fostering the emancipation of smallholders, development actors promote a labor-intensive and unprofitable way of farming that exploits local resources for the sake of green agendas and white markets. This article highlights the need for a critical reflection on the potential limitations of agroecology and calls for a more nuanced approach that considers the complex realities of smallholders in West Africa.

Published
2023
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185. Agent-Based Mixed Reality Environments in Healthcare: The Smart Shock Room Project

Author

Croatti, Angelo, Bottazzi, Manuel, Ricci, Alessandro, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Demazeau, Yves, editor, Holvoet, Tom, editor, Corchado, Juan M., editor, and Costantini, Stefania, editor

Published
2020
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188. Modulation of diabetes-related retinal pathophysiology by PTX3.

Author

Pathak, Varun, Bertelli, Pietro M., Pedrini, Edoardo, Harkin, Kevin, Peixoto, Elisa, Allen, Lynsey-Dawn, Mcloughlin, Kiran, Chavda, Natasha D., Hamill, Kevin J., Guduric-Fuchs, Jasenka, Inforzato, Antonio, Bottazzi, Barbara, Stitt, Alan W., and Medina, Reinhold J.

Subjects
VISION, DIABETIC retinopathy, DIABETES complications, DISEASE progression, TISSUE remodeling
Abstract

Diabetic retinopathy (DR) is a common complication of diabetes characterized by vascular pathology and neuroinflammation. Pentraxin 3 (PTX3) is a soluble pattern recognition molecule that functions at the crossroads between innate immunity, inflammation, and tissue remodeling. DR is known to involve inflammatory pathways, although the potential relevance of PTX3 has not been explored. We found that PTX3 protein levels increased in the retina of diabetic mice. Similarly, evaluation of a publicly available transcriptomic human dataset revealed increased PTX3 expression in DR with diabetic macular edema and proliferative retinopathy, when compared to nondiabetic retinas or diabetic retinas without complications. To further understand the role of PTX3 within DR, we employed the streptozotocin-induced diabetes model in PTX3 knockout mice (PTX3KO), which were followed up for 9 mo to evaluate hallmarks of disease progression. In diabetic PTX3KO mice, we observed decreased reactive gliosis, diminished microglia activation, and reduced vasodegeneration, when compared to diabetic PTX3 wild-type littermates. The decrease in DR-associated pathological features in PTX3KO retinas translated into preserved visual function, as evidenced by improved optokinetic response, restored b-wave amplitude in electroretinograms, and attenuated neurodegeneration. We showed that PTX3 induced an inflammatory phenotype in human retinal macroglia, characterized by GFAP upregulation and increased secretion of IL6 and PAI-1. We confirmed that PTX3 was required for TNF-α-induced reactive gliosis, as PTX3KO retinal explants did not up-regulate GFAP in response to TNF-α. This study reveals a unique role for PTX3 as an enhancer of sterile inflammation in DR, which drives pathogenesis and ultimately visual impairment. [ABSTRACT FROM AUTHOR]

Published
2024
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190. A Serum Multi-Parametric Analysis Identifies an Early Innate Immune Signature Associated to Increased Vaccine-Specific Antibody Production and Seroconversion in Simultaneous COVID-19 mRNA and Cell-Based Quadrivalent Influenza Vaccination.

Author

Severa, Martina, Ricci, Daniela, Etna, Marilena Paola, Facchini, Marzia, Puzelli, Simona, Fedele, Giorgio, Iorio, Egidio, Cairo, Giada, Castrechini, Sara, Ungari, Valentina, Iannetta, Marco, Leone, Pasqualina, Chirico, Mattea, Pisanu, Maria Elena, Bottazzi, Barbara, Benedetti, Livia, Sali, Michela, Bartolomucci, Remo, Balducci, Stefano, and Garlanda, Cecilia

Subjects
TYPE 2 diabetes, IMMUNE serums, ANTIBODY titer, OXIDATION of glucose, HUMORAL immunity
Abstract

In this pilot study, a multi-parametric analysis comparing immune responses in sera of adult healthy subjects (HS) or people with type 2 diabetes mellitus (T2D) undergoing the single or simultaneous administration of mRNA-based COVID-19 and cellular quadrivalent inactivated influenza vaccines was conducted. While SARS-CoV-2 antibodies remains comparable, influenza antibody titers and seroconversion were significantly higher upon simultaneous vaccination. Magnitude of anti-influenza humoral response closely correlated with an early innate immune signature, previously described for the COVID-19 vaccine, composed of IL-15, IL-6, TNF-α, IFN-γ, CXCL-10 and here extended also to acute-phase protein Pentraxin 3. People with T2D receiving simultaneous vaccination showed a protective response comparable to HS correlating with the early induction of IFN-γ/CXCL10 and a significant reduction of the circulating glucose level due to increased oxidation of glucose digestion and consumption. These data, although preliminary and in-need of validation in larger cohorts, might be exploited to optimize future vaccination in people with chronic disorders, including diabetes. [ABSTRACT FROM AUTHOR]

Published
2024
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191. Optimization of Cellular Transduction by the HIV-Based Pseudovirus Platform with Pan-Coronavirus Spike Proteins.

Author

Thimmiraju, Syamala Rani, Villar, Maria Jose, Kimata, Jason T., Strych, Ulrich, Bottazzi, Maria Elena, Hotez, Peter J., and Pollet, Jeroen

Subjects
CORONAVIRUS spike protein, TRANSGENE expression, CATIONIC polymers, SARS-CoV-2, CORONAVIRUSES
Abstract

Over the past three years, new SARS-CoV-2 variants have continuously emerged, evolving to a point where an immune response against the original vaccine no longer provided optimal protection against these new strains. During this time, high-throughput neutralization assays based on pseudoviruses have become a valuable tool for assessing the efficacy of new vaccines, screening updated vaccine candidates against emerging variants, and testing the efficacy of new therapeutics such as monoclonal antibodies. Lentiviral vectors derived from HIV-1 are popular for developing pseudo and chimeric viruses due to their ease of use, stability, and long-term transgene expression. However, the HIV-based platform has lower transduction rates for pseudotyping coronavirus spike proteins than other pseudovirus platforms, necessitating more optimized methods. As the SARS-CoV-2 virus evolved, we produced over 18 variants of the spike protein for pseudotyping with an HIV-based vector, optimizing experimental parameters for their production and transduction. In this article, we present key parameters that were assessed to improve such technology, including (a) the timing and method of collection of pseudovirus supernatant; (b) the timing of host cell transduction; (c) cell culture media replenishment after pseudovirus adsorption; and (d) the centrifugation (spinoculation) parameters of the host cell+ pseudovirus mix, towards improved transduction. Additionally, we found that, for some pseudoviruses, the addition of a cationic polymer (polybrene) to the culture medium improved the transduction process. These findings were applicable across variant spike pseudoviruses that include not only SARS-CoV-2 variants, but also SARS, MERS, Alpha Coronavirus (NL-63), and bat-like coronaviruses. In summary, we present improvements in transduction efficiency, which can broaden the dynamic range of the pseudovirus titration and neutralization assays. [ABSTRACT FROM AUTHOR]

Published
2024
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192. What Is the Economic Benefit of Annual COVID-19 Vaccination From the Adult Individual Perspective?

Author

Bartsch, Sarah M, O'Shea, Kelly J, Weatherwax, Colleen, Strych, Ulrich, Velmurugan, Kavya, John, Danielle C, Bottazzi, Maria Elena, Hussein, Mustafa, Martinez, Marie F, Chin, Kevin L, Ciciriello, Allan, Heneghan, Jessie, Dibbs, Alexis, Scannell, Sheryl A, Hotez, Peter J, and Lee, Bruce Y

Subjects
SARS-CoV-2, COVID-19, SARS-CoV-2 Omicron variant, VACCINE effectiveness, MONETARY incentives
Abstract

Background With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward. Methods We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine. Results For an 18–49 year old, getting vaccinated at its current price ($60) can save the individual on average $ 30–$603 if the individual is uninsured and $4–$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023–2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50–64 year old, these cost-savings increase to $111–$1278 and $119–$1706 for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% preexisting protection against infection (eg, vaccinated 9 months earlier). Conclusions There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year. [ABSTRACT FROM AUTHOR]

Published
2024
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193. Vaccine-linked chemotherapy induces IL-17 production and reduces cardiac pathology during acute Trypanosoma cruzi infection

Author

Julio V. Cruz-Chan, Liliana E. Villanueva-Lizama, Leroy Versteeg, Ashish Damania, Maria José Villar, Cristina González-López, Brian Keegan, Jeroen Pollet, Fabian Gusovsky, Peter J. Hotez, Maria Elena Bottazzi, and Kathryn M. Jones

Subjects
Medicine, Science
Abstract

Abstract Chagas disease resulting from Trypanosoma cruzi infection leads to a silent, long-lasting chronic neglected tropical disease affecting the poorest and underserved populations around the world. Antiparasitic treatment with benznidazole does not prevent disease progression or death in patients with established cardiac disease. Our consortium is developing a therapeutic vaccine based on the T. cruzi flagellar—derived antigen Tc24-C4 formulated with a Toll-like receptor 4 agonist adjuvant, to complement existing chemotherapy and improve treatment efficacy. Here we demonstrate that therapeutic treatment of acutely infected mice with a reduced dose of benznidazole concurrently with vaccine treatment – also known as “vaccine-linked chemotherapy”—induced a TH17 like immune response, with significantly increased production of antigen specific IL-17A, IL-23 and IL-22, and CD8 + T lymphocytes, as well as significantly increased T. cruzi specific IFNγ-producing CD4 + T lymphocytes. Significantly reduced cardiac inflammation, fibrosis, and parasite burdens and improved survival were achieved by vaccine-linked chemotherapy and individual treatments. Importantly, low dose treatments were comparably efficacious to high dose treatments, demonstrating potential dose sparing effects. We conclude that through induction of TH17 immune responses vaccine-linked chemotherapeutic strategies could bridge the tolerability and efficacy gaps of current drug treatment in Chagasic patients.

Published
2021
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194. Lancet COVID-19 Commission Statement on the occasion of the 75th session of the UN General Assembly

Author

Sachs, Jeffrey D, Abdool Karim, Salim, Aknin, Lara, Allen, Joseph, Brosbøl, Kirsten, Cuevas Barron, Gabriela, Daszak, Peter, Espinosa, María Fernanda, Gaspar, Vitor, Gaviria, Alejandro, Haines, Andy, Hotez, Peter, Koundouri, Phoebe, Larraín Bascuñán, Felipe, Lee, Jong-Koo, Pate, Muhammad, Polman, Paul, Reddy, Srinath, Serageldin, Ismail, Shah, Raj, Thwaites, John, Vike-Freiberga, Vaira, Wang, Chen, Were, Miriam Khamadi, Xue, Lan, Zhu, Min, Bahadur, Chandrika, Bottazzi, Maria Elena, Ben Amor, Yanis, Barredo, Lauren, Karadag Caman, Ozge, Lafortune, Guillaume, Torres, Emma, Ethridge, Ismini, and Bartels, Juliana G E

Published
2020
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