9 results on '"Chiara Boarini"'
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2. Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro
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Marzia Rossi, Andrea Vecchi, Camilla Tiezzi, Valeria Barili, Paola Fisicaro, Amalia Penna, Ilaria Montali, Stephane Daffis, Simon P Fletcher, Anuj Gaggar, Jonathan Medley, Michael Graupe, Latesh Lad, Alessandro Loglio, Roberta Soffredini, Marta Borghi, Teresa Pollicino, Cristina Musolino, Arianna Alfieri, Federica Brillo, Diletta Laccabue, Marco Massari, Chiara Boarini, Gianluca Abbati, Giuseppe Pedrazzi, Gabriele Missale, Pietro Lampertico, Carlo Ferrari, and Carolina Boni
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Gastroenterology - Abstract
ObjectiveExhausted hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection are broadly heterogeneous. Characterisation of their functional impairment may allow to distinguish patients with different capacity to control infection and reconstitute antiviral function.DesignHBV dextramer+CD8 T cells were analysed ex vivo for coexpression of checkpoint/differentiation markers, transcription factors and cytokines in 35 patients with HLA-A2+chronic hepatitis B (CHB) and in 29 control HBsAg negative CHB patients who seroconverted after NUC treatment or spontaneously. Cytokine production was also evaluated in HBV peptide-stimulated T cell cultures, in the presence or absence of antioxidant, polyphenolic, PD-1/PD-L1 inhibitor and TLR-8 agonist compounds and the effect on HBV-specific responses was further validated on additional 24 HLA-A2 negative CHB patients.ResultsSeverely exhausted HBV-specific CD8 T cell subsets with high expression of inhibitory receptors, such as PD-1, TOX and CD39, were detected only in a subgroup of chronic viraemic patients. Conversely, a large predominance of functionally more efficient HBV-specific CD8 T cell subsets with lower expression of coinhibitory molecules and better response to in vitro immune modulation, typically detected after resolution of infection, was also observed in a proportion of chronic viraemic HBV patients. Importantly, the same subset of patients who responded more efficiently to in vitro immune modulation identified by HBV-specific CD8 T cell analysis were also identified by staining total CD8 T cells with PD-1, TOX, CD127 and Bcl-2.ConclusionsThe possibility to distinguish patient cohorts with different capacity to respond to immune modulatory compounds in vitro by a simple analysis of the phenotypic CD8 T cell exhaustion profile deserves evaluation of its clinical applicability.
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- 2023
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3. Safety and efficacy of sucrosomal iron in inflammatory bowel disease patients with iron deficiency anemia
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Elena Buzzetti, Federica Incerti, Gianluca Abbati, Paolo Ventura, Chiara Boarini, Davide Bocchi, Antonello Pietrangelo, and Francesca Pileri
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Adult ,Male ,medicine.medical_specialty ,Anemia ,Iron ,030204 cardiovascular system & hematology ,Inflammatory bowel disease ,Gastroenterology ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Hepcidins ,Hepcidin ,Internal medicine ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Adverse effect ,biology ,Anemia, Iron-Deficiency ,business.industry ,Middle Aged ,IBD, Iron, Sucrosomial, Anemia. Hepcidin ,medicine.disease ,Inflammatory Bowel Diseases ,Ulcerative colitis ,digestive system diseases ,Regimen ,Tolerability ,Iron-deficiency anemia ,Emergency Medicine ,biology.protein ,Colitis, Ulcerative ,Female ,business - Abstract
Iron deficiency anemia (IDA) is one of the most common complications of inflammatory bowel disease (IBD). We planned a prospective study to address tolerability and efficacy of sucrosomial iron, a new oral formulation of ferric pyrophosphate, in IBD patients. Thirty patients with a confirmed diagnosis of Crohn’s Disease (CD) or ulcerative colitis (UC) and mild IDA were enrolled. Patients with severe IBD were excluded. All patients underwent 12 weeks of oral treatment with 30 mg/day of sucrosomial iron. Treatment compliance and adverse events were investigated every 4 weeks. Iron status, hematological parameters and IBD activity scores were determined at baseline and at the end of treatment, as well as serum hepcidin and non-transferrin bound iron (NTBI) levels. Twenty-four (80%) patients took more than 90% of the prescribed regimen. Forty-four adverse events (AEs) were recorded, but none of them is considered certainly or probably related to the study treatment. Interestingly, only eleven gastrointestinal events were recorded in 9 (30%) patients. At the end of treatment, all iron parameters improved significantly and Hb increased in 86% of patients (from 11.67 to 12.37 g/dl, p = 0.001). Serum hepcidin showed a significant increase in 79% of patients and became positively correlated with C-reactive protein (CRP) at the end of the study, while NTBI remained below the detection threshold after iron supplementation. The IBD activity scores improved in both CD and UC. This pilot interventional study supports the therapeutic use of sucrosomial iron in IBD and paves the way for future studies in larger or more difficult IBD populations.
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- 2019
4. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis
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Giada Carolo, Veronica Bernabucci, Luchino Chessa, Maria Luisa Russo, Giorgio Maria Saracco, Marzia Montalbano, Barbara Menzaghi, Giovanni Di Perri, Adriano Lazzarin, Silvia La Monica, Raffaele Bruno, Gian Ludovico Rapaccini, Mario U. Mondelli, Anna Maria Schimizzi, Caterina Pasquazzi, Maurizia Rossana Brunetto, Antonio Craxì, Filomena Morisco, Carmela Lo Guercio, Vania Giacomet, Alessia Giorgini, Mario Masarone, Francesca Paolo Russo, T. Zolfino, Vincenzo Sangiovanni, Alessia Ciancio, Antonella d'Arminio Monforte, Savino Bruno, E.M. Erne, Antonio Gasbarrini, Francesco Castelli, Sergio Novara, G. Nardone, Andrea De Luca, Claudio Maria Mastroianni, Gioacchino Angarano, Chiara Dentone, Renato Maserati, Anna Maria Piscaglia, Tiziana Quirino, Giuseppe Tarantino, M. Lichtner, Antonio Chirianni, Giuseppina Brancaccio, S. Paganin, Alfredo Alberti, Silvia Corradori, Edoardo G. Giannini, Carlo Torti, Chiara Boarini, Raffaele Cozzolongo, Marco Di Stefano, Alessandro Soria, Paolo Tundi, Giovanni Cassola, Debora Angrisani, Antonio Grieco, Cecilia Pravadelli, Giuliano Rizzardini, Roberto Gulminetti, Vincenzo Messina, Maria Rendina, Massimo Pirisi, Irene Cacciola, Roberto Ganga, Raffaella Lionetti, Paolo Calabrese, Laura Ponti, Filomena Simeone, Maurizio Russello, Monica Monti, Nicola Boffa, Pierluigi Tarquini, Franco Capra, Ivo Avancini, Domenico Sansonno, Stefano Fagiuoli, Michele Barone, Giacomo Vecchiet, Salvatore Rizzo, Carlo Federico Perno, Teresa Santantonio, Pierluigi Toniutto, Massimo Zuin, Nicola Caporaso, Alessandra Orlandini, Grazielle Marie Pigozzi, Martina Felder, Antonio Cristaudo, Roberto Cecere, Massimo Marignani, Vincenza Calvaruso, G. Abbati, Domenico Potenza, Maria Chiara Piras, Mario Rizzetto, Serena Cima, Marco delle Monache, Alessio Aghemo, D. Ieluzzi, Guglielmo Borgia, Giampaolo Corti, Paolo Poggio, Manuela Merli, Elena Danieli, Andrea Giacometti, Massimo Andreoni, Antonino Picciotto, Mario Angelico, Benedetta Canovari, Sara Piovesan, Anna Linda Zignego, Antonio Benedetti, Emanuele Durante, Erica Villa, Marcello Persico, Antonio Patrizio Termite, Barbara Coco, Maria Vinci, Lucio Boglione, Cristina Rossi, Paolo Angeli, Massimo Memoli, Maria Teresa Giordani, Massimo De Luca, Luisa Pasulo, Vincenzo Vullo, Mario Melazzini, Attilio Solinas, Pietro Gatti, Michele Guerra, Silvia Martini, Antonio Ascione, Massimo Puoti, Roberto Cauda, Giovanna Onnelli, Silvia Magnani, Salvatore Madonna, Giovanni Raimondo, Marco Tabone, Gloria Taliani, Dante Romagnoli, Aldo Marrone, Umberto Vespasiani Gentilucci, Luca Miele, Marcello Tavio, Andrea Antinori, Giampiero D'Offizi, Mirella Onofrio, Valentina Iodice, Lucio Cosco, Guido Piai, Luca Pani, Francesca Ceccherini Silberstein, Simona Montilla, Marco Lenzi, Luca Fontanella, Alessandro Federico, Carlo Ferrari, Giustino Parruti, Antonio Di Biagio, Gabriella Verucchi, Fabio Marsetti, Michele Milella, Maria Grazia Rumi, Antonio Izzi, Marco Marzioni, Francesca Donato, Vanni Borghi, Mariano Quartini, Massimo Colombo, Michele Imparato, Giovanni Battista Gaeta, P.L. Blanc, Alfredo Di Leo, Nicola Coppola, Alessandro Chiodera, Ivana Maida, Davide Campagnolo, Cinzia Antonini, Antonietta Romano, A. Gianstefani, Katia Falasca, Massimo Levrero, Gaetano Serviddio, Maria Paola Trotta, Olivia Morelli, Salvatore Petta, Elisabetta Teti, Maria Rita Parisi, Pietro Andreone, Ascione, Antonio, De Luca, Massimo, Melazzini, Mario, Montilla, Simona, Trotta, Maria Paola, Petta, Salvatore, Puoti, Massimo, Sangiovanni, Vincenzo, Messina, Vincenzo, Bruno, Savino, Izzi, Antonio, Villa, Erica, Aghemo, Alessio, Zignego, Anna Linda, Orlandini, Alessandra, Fontanella, Luca, Gasbarrini, Antonio, Marzioni, Marco, Giannini, Edoardo G., Craxì, Antonio, Abbati, Giuseppe, Alberti, Alfredo, Andreone, Pietro, Andreoni, Massimo, Angeli, Paolo, Angelico, Mario, Angarano, Gioacchino, Angrisani, Debora, Antinori, Andrea, Antonini, Cinzia, Avancini, Ivo, Barone, Michele, Bruno, Raffaele, Benedetti, Antonio, Bernabucci, Veronica, Blanc, Pier, Boarini, Chiara, Boffa, Nicola, Boglione, Lucio, Borghi, Vanni, Borgia, Guglielmo, Brancaccio, Giuseppina, Brunetto, Maurizia, Cacciola, Irene, Calabrese, Paolo, Calvaruso, Vincenza, Campagnolo, Davide, Canovari, Benedetta, Caporaso, Nicola, Capra, Franco, Carolo, Giada, Cassola, Giovanni, Castelli, Francesco, Cauda, Roberto, Silberstein, Francesca Ceccherini, Cecere, Roberto, Chessa, Luchino, Chiodera, Alessandro, Chirianni, Antonio, Ciancio, Alessia, Cima, Serena, Coco, Barbara, Colombo, Massimo, Coppola, Nicola, Corti, Giampaolo, Cosco, Lucio, Corradori, Silvia, Cozzolongo, Raffaele, Cristaudo, Antonio, Danieli, Elena, Monforte, Antonella D’Arminio, Monache, Marco delle, Del Poggio, Paolo, de Luca, Andrea, Dentone, Chiara, Di Biagio, Antonio, Di Leo, Alfredo, Di Perri, Giovanni, Di Stefano, Marco, D’Offizi, Giampiero, Donato, Francesca, Durante, Emanuele, Erne, Elke, Fagiuoli, Stefano, Falasca, Katia, Federico, Alessandro, Felder, Martina, Ferrari, Carlo, Gaeta, Giovanni Battista, Ganga, Roberto, Gatti, Pietro, Giacomet, Vania, Giacometti, Andrea, Gianstefani, Alice, Giordani, Maria, Giorgini, Alessia, Grieco, Antonio, Guerra, Michele, Gulminetti, Roberto, Ieluzzi, Donatella, Imparato, Michele, Iodice, Valentina, La Monica, Silvia, Lazzarin, Adriano, Lenzi, Marco, Levrero, Massimo, Lichtner, Myriam, Lionetti, Raffaella, Guercio, Carmela Lo, Madonna, Salvatore, Magnani, Silvia, Maida, Ivana, Marignani, Massimo, Marrone, Aldo, Marsetti, Fabio, Martini, Silvia, Masarone, Mario, Maserati, Renato, Mastroianni, Claudio Maria, Memoli, Massimo, Menzaghi, Barbara, Merli, Manuela, Miele, Luca, Milella, Michele, Mondelli, Mario, Montalbano, Marzia, Monti, Monica, Morelli, Olivia, Morisco, Filomena, Nardone, Gaetano, Novara, Sergio, Onnelli, Giovanna, Onofrio, Mirella, Paganin, Simona, Pani, Luca, Parisi, Maria Rita, Parruti, Giustino, Pasquazzi, Caterina, Pasulo, Luisa, Perno, Carlo Federico, Persico, Marcello, Piai, Guido, Picciotto, Antonino, Pigozzi, Grazielle Marie, Piovesan, Sara, Piras, Maria Chiara, Pirisi, Massimo, Piscaglia, Anna Maria, Ponti, Laura, Potenza, Domenico, Pravadelli, Cecilia, Quartini, Mariano, Quirino, Tiziana, Raimondo, Giovanni, Rapaccini, Gian Ludovico, Rendina, Maria, Rizzardini, Giuliano, Rizzetto, Mario, Rizzo, Salvatore, Romagnoli, Dante, Romano, Antonietta, Rossi, Cristina, Rumi, Maria Grazia, Russello, Maurizio, Russo, Francesca Paolo, Russo, Maria Luisa, Sansonno, Domenico Ettore, Santantonio, Teresa Antonia, Saracco, Giorgio, Schimizzi, Anna Maria, Serviddio, Gaetano, Simeone, Filomena, Solinas, Attilio, Soria, Alessandro, Tabone, Marco, Taliani, Gloria, Tarantino, Giuseppe, Tarquini, Pierluigi, Tavio, Marcello, Termite, Antonio, Teti, Elisabetta, Toniutto, Pierluigi, Torti, Carlo, Tundi, Paolo, Vecchiet, Giacomo, Verucchi, Gabriella, Gentilucci, Umberto Vespasiani, Vinci, Maria, Vullo, Vincenzo, Zolfino, Teresa, Zuin, Massimo, Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, and Zuin, M
- Subjects
Cyclopropanes ,Liver Cirrhosis ,Male ,Cirrhosis ,Dasabuvir ,Elderly ,Ombitasvir ,Paritaprevir ,Aged ,80 and over ,Anilides ,Antiviral Agents ,Biomarkers ,Carbamates ,Female ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Macrocyclic Compounds ,Ribavirin ,Ritonavir ,Sulfonamides ,Treatment Outcome ,Uracil ,Drug Therapy ,Combination ,Genotype ,Cirrhosis, Dasabuvir, Elderly, Ombitasvir, Paritaprevir, Microbiology (medical), Infectious Diseases ,Aged, 80 and over ,Hepatitis C, Chronic ,Drug Therapy, Combination ,Microbiology (medical) ,Infectious Diseases ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,2-Naphthylamine ,Medicine ,030212 general & internal medicine ,Valine ,General Medicine ,030211 gastroenterology & hepatology ,Macrocyclic Compound ,medicine.drug ,Human ,medicine.medical_specialty ,Proline ,Lactams, Macrocyclic ,Settore MED/12 - GASTROENTEROLOGIA ,Liver Cirrhosi ,Sulfonamide ,03 medical and health sciences ,Internal medicine ,Decompensation ,Hepatitis ,Antiviral Agent ,Cirrhosi ,Hepaciviru ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Anilide ,Biomarker ,medicine.disease ,chemistry ,Carbamate ,business - Abstract
Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.
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- 2018
5. Micellar-type complexes of tailor-made synthetic block copolymers containing the HIV-1 tat DNA for vaccine application
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Angela Bonaccorsi, Katia Sparnacci, Chiara Boarini, Giuseppe Altavilla, Marco Marchisio, Michele Laus, Barbara Ensoli, Luisa Tondelli, Stefano Buttò, Monica Betti, and Antonella Caputo
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HIV-1 tat gene delivery and expression ,SafetyToxicity ,Gene Expression ,Gene delivery ,Micelle ,Polyethylene Glycols ,NO ,Mice ,chemistry.chemical_compound ,PEG ratio ,Vaccines, DNA ,Animals ,Deoxyribonuclease I ,Humans ,Micelles ,AIDS Vaccines ,Drug Carriers ,Mice, Inbred BALB C ,Block copolymers ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,Cationic polymerization ,Combinatorial chemistry ,Nylons ,Infectious Diseases ,chemistry ,Biochemistry ,Gene Products, tat ,HIV-1 ,Methacrylates ,Molecular Medicine ,tat Gene Products, Human Immunodeficiency Virus ,Drug carrier ,Ethylene glycol ,DNA - Abstract
A novel class of cationic block copolymers constituted by a neutral hydrophilic poly(ethylene glycol) (PEG) block and a positively charged poly(dimethylamino)ethyl methacrylate block was prepared for delivery of DNA. These block copolymers spontaneously assemble with DNA to give in aqueous medium micellar-like structures. Five of these novel block copolymers (K1-5), differing in the length of both the PEG chain and the linear charge density of the poly(dimethylamino)ethyl methacrylate block, were prepared and analyzed for gene delivery, gene expression and safety. All five block copolymers protected DNA from DNAse I digestion and delivered the DNA into the cell. However, only three of them (K1, K2 and K5) released the DNA at level allowing efficient gene expression into cells. No toxic effects of both the copolymers alone or their DNA complexes were observed in vitro or in mice. In addition, copolymers were scarcely immunogenic. These results indicate that this novel class of cationic block copolymers is safe and possesses the biological characteristics required for DNA delivery, thus, representing promising vehicles for DNA vaccination.
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- 2002
- Full Text
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6. DNA Immunization with HIV-1tatMutated in thetransActivation Domain Induces Humoral and Cellular Immune Responses Against Wild-Type Tat
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Elisabetta Caselli, Monica Betti, Maria Pia Grossi, Pier Giorgio Balboni, Cristina Rossi, Chiara Boarini, Aurelio Cafaro, Giuseppe Barbanti-Brodano, Barbara Ensoli, and Antonella Caputo
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Immunology ,Immunology and Allergy - Abstract
Intramuscular immunization of mice with plasmids encoding two transdominant negative mutants of the HIV-1 Tat protein (Tat22 and Tat22/37) elicited a humoral response to wild-type Tat that is comparable to that induced by inoculation of wild-type tat DNA or Tat protein. The percentage of the responders and the Ab titers continued to increase after three additional DNA boosts and pretreatment with bupivacaine at the site of inoculation, without a significant difference (p > 0.05) among the three groups of mice immunized with mutant and wild-type tat genes. By utilizing synthetic peptides representing the amino acid sequence of Tat, one major B cell epitope was defined within the cysteine-rich domain of Tat. Anti-Tat IgG Abs directed against this epitope were found in mice immunized with all tat DNA constructs, whereas different Tat epitopes were detected in mice immunized with the Tat protein. Similarly, IgG2a was the predominant isotype in DNA-immunized mice, with both mutants and wild-type tat genes, as compared with protein immunization, which induced mostly IgG1 and IgG3. Sera from most immunized mice neutralized the effect of extracellular Tat in activating HIV-1 replication. A cellular response was also elicited as indicated by the proliferation of splenocytes when stimulated with wild-type Tat. These results indicate that the wild-type Tat Ag is recognized by Abs and T cells induced by DNA immunization with mutated tat genes, suggesting the possible use of these Tat transdominant mutants, lacking viral trans activation activity and capable of blocking wild-type Tat activity, in the development of an anti-HIV-1 vaccine.
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- 1999
- Full Text
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7. Immunization with low doses of HIV-1 tat DNA delivered by novel cationic block copolymers induces CTL responses against Tat
- Author
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Antonella Caputo, Riccardo Gavioli, Chiara Boarini, Giuseppe Altavilla, Fabiola Micheletti, Franco Lorenzini, Arianna Castaldello, Luisa Tondelli, Monica Betti, Egidio Brocca-Cofano, Aurelio Cafaro, Michele Laus, Barbara Ensoli, and Katia Sparnacci
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Cellular immunity ,Recombinant Fusion Proteins ,Biology ,HIV Antibodies ,Lymphocyte Activation ,Transfection ,Injections, Intramuscular ,DNA vaccination ,Polyethylene Glycols ,chemistry.chemical_compound ,Mice ,Antibody Specificity ,Cations ,Vaccines, DNA ,Cytotoxic T cell ,Animals ,Deoxyribonuclease I ,Enzyme Inhibitors ,AIDS Vaccines ,Drug Carriers ,Immunity, Cellular ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,Vaccination ,Public Health, Environmental and Occupational Health ,Fibroblasts ,biology.organism_classification ,Virology ,CTL ,Nylons ,Infectious Diseases ,chemistry ,Naked DNA ,Genes, tat ,Delayed-Action Preparations ,Lentivirus ,Gene Products, tat ,HIV-1 ,Molecular Medicine ,Methacrylates ,Female ,tat Gene Products, Human Immunodeficiency Virus ,DNA ,Spleen ,T-Lymphocytes, Cytotoxic - Abstract
Cytotoxic T cell responses are key to the control of intracellular pathogens including HIV-1. In particular, HIV-1 vaccines based on regulatory proteins, such as Tat, are aimed at controlling HIV-1 replication and at blocking disease development by inducing cytotoxic T cell responses. Naked DNA is capable of inducing such responses but it requires several inoculations of high amounts of DNA, and/or prime-boost regimens. Here, we show that a novel class of cationic block copolymers protect the DNA from DNAse I digestion, and improve DNA delivery to antigen-presenting cells (APCs) after intramuscular (i.m.) vaccination. In particular, three cationic block copolymers (K1, K2 and K5) were used to deliver the HIV-1 pCV-tat DNA vaccine in BALB/c mice. The results indicate that vaccination with a very low dose (1 microg) of pCV-tat delivered by the cationic block copolymer K2 is safe and, as compared to naked DNA (up to 30 microg), greatly increases the CTL response against Tat, which was detected in all animals in the absence or in the presence of re-stimulation.
- Published
- 2003
8. Characterization of HIV-1 Tat proteins mutated in the transactivation domain for prophylactic and therapeutic application
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Marco Marchisio, Rebecca Voltan, Filomena Nappi, Irene Mantovani, Chiara Boarini, Antonella Caputo, Barbara Ensoli, and Monica Betti
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Transcriptional Activation ,Genes, Viral ,Recombinant Fusion Proteins ,HIV Infections ,Biology ,medicine.disease_cause ,Transfection ,Virus ,Cell Line ,Transactivation ,Mice ,Immune system ,medicine ,Animals ,Humans ,HIV-1 Tat ,Gene ,AIDS Vaccines ,Mutation ,General Veterinary ,General Immunology and Microbiology ,Public Health, Environmental and Occupational Health ,biology.organism_classification ,Virology ,Infectious Diseases ,Cell culture ,Lentivirus ,Gene Products, tat ,HIV-1 ,Molecular Medicine ,tat Gene Products, Human Immunodeficiency Virus - Abstract
Previous work from our group showed that genetic immunization of mice with HIV-1 tat genes (tat22 and tat22/37), encoding Tat proteins mutated in the transactivation domain and lacking Tat-transactivating activity, evoke an immune response to wild-type Tat, both humoral and cellular. In the present work we report that the mutated Tat proteins localize within the cells, are released and taken up by the cells in a fashion similar to wild-type Tat. Moreover, the exogenous mutated Tat proteins interfere with the transactivating function of extracellular wild-type Tat. These results support the notion that tat22 and tat22/37 genes may represent good candidates for the development of an anti-HIV-1 vaccine, especially for HIV-1 infected patients.
- Published
- 2001
9. Transiently transfected and stably integrated HIV-1 LTR responds differentially to the silencing activity of the Kruppel-associated box (KRAB) transcriptional repressor domain
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Antonella Caputo, Giuseppe Barbanti-Brodano, C Rossi, Chiara Boarini, Monica Betti, Luigi Lania, Gina Pengue, and Davide Gibellini
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Gene Expression Regulation, Viral ,Transcription, Genetic ,Recombinant Fusion Proteins ,Virus Integration ,Kruppel-Like Transcription Factors ,Biology ,Transfection ,Jurkat cells ,Cell Line ,NO ,Jurkat Cells ,Virology ,Transcriptional regulation ,Animals ,Humans ,Gene silencing ,HIV Long Terminal Repeat ,Zinc finger ,HIV-1 Tat mutants ,Expression vector ,KRAB ,Zinc Fingers ,HIV-1 replication ,Kruppel-associated box ,Molecular biology ,Fusion protein ,Long terminal repeat ,DNA-Binding Proteins ,Repressor Proteins ,HIV-1, KRAB, transient transfection ,Infectious Diseases ,Gene Products, tat ,Mutation ,HIV-1 ,transient transfection ,HeLa Cells ,Transcription Factors - Abstract
It has been demonstrated previously that the transcriptional repressor domain called the Krüppel-associated box (KRAB), conserved in a large number of Krüppel-type zinc finger proteins, fused to Tat transdominant negative mutants, is able to silence HIV-1 long terminal repeat (LTR)-driven gene expression in transient transfection assays. In the present study chimeric Tat mutant-KRAB retroviral expression vectors were used to control HIV-1 replication in acutely infected cells. It was found that while transient and stable expression of Tat mutant-KRAB chimeric proteins represses HIV-1 LTR-driven gene transcription in transient assays, stable expression of Tat mutant-KRAB chimeric molecules does not confer resistance to HIV-1 infection in Jurkat T lymphocytic cell lines. The results provide further evidence that transient transfection may underestimate the role of chromosomal structure in transcriptional regulation and highlight the caveat of direct extrapolation of transient results for designing gene therapy strategies for efficient control of HIV-1 infection.
- Published
- 1999
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