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Article ; Online: Brief Report: In cART-Treated HIV-Infected Patients, Immunologic Failure Is Associated With a High Myeloid-Derived Suppressor Cell Frequency.

Grassi, Germana / Notari, Stefania / Cicalini, Stefania / Casetti, Rita / Cimini, Eleonora / Bordoni, Veronica / Gagliardini, Roberta / Mazzotta, Valentina / Antinori, Andrea / Agrati, Chiara / Sacchi, Alessandra

Journal of acquired immune deficiency syndromes (1999)

2024 Volume 95, Issue 2, Page(s) 185–189

Abstract: Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral ... ...

Abstract	Background: During HIV infection, effective combined antiretroviral therapy suppresses viral replication and restores the number of circulating CD4+ T cells. However, 15%-30% of treated patients show a discordant response to combined antiretroviral therapy. Myeloid-derived suppressor cells (MDSC) are expanded in HIV+ patients; to better understand the role of MDSC on CD4 T-cell recovery, we evaluated the frequency of MDSC in HIV+ patients under combined antiretroviral therapy and its association with immunologic response. Methods: We enrolled 60 HIV+ patients, including complete responders (R, n = 44), virologic nonresponders (VNR, n = 5), and immunologic nonresponders (INR, n = 11). The frequency of circulating MDSC and the percentage of activated and naïve CD4 T cells were evaluated by flow cytometry. Plasmatic cytokine levels were analyzed by automated ELISA. Results: As previously observed, polymorphonuclear MDSC (PMN-MDSC) frequency was higher in HIV+ patients compared with healthy donors. Furthermore, PMN-MDSC percentage was higher in INR than R patients, and a significant association between MDSC frequency and immunologic failure was confirmed by a receiver operator characteristic analysis. Accordingly, an inverse correlation was found between the percentages of PMN-MDSC and naïve CD4 T cells. A positive correlation was observed between PMN-MDSC frequency and the percentage of human leucocyte antigen locus DR + CD4 T cells and the plasmatic level of IL-1β and IL-8. Conclusion: Our results show that a high frequency of PMN-MDSC persists in INR, possibly because of immune activation, contributing to CD4 T-cell recovery failure. These findings further highlight the detrimental role of MDSC during HIV infection, suggesting these cells as a possible new therapeutic target.
MeSH term(s)	Humans ; Myeloid-Derived Suppressor Cells ; HIV Infections ; CD4-Positive T-Lymphocytes ; Cytokines ; Enzyme-Linked Immunosorbent Assay
Chemical Substances	Cytokines
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000003335
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Article: In Acute Dengue Infection, High TIM-3 Expression May Contribute to the Impairment of IFNγ Production by Circulating Vδ2 T Cells

Cimini, Eleonora / Grassi, Germana / Beccacece, Alessia / Casetti, Rita / Castilletti, Concetta / Capobianchi, Maria Rosaria / Nicastri, Emanuele / Agrati, Chiara

Viruses. 2022 Jan. 12, v. 14, no. 1

2022

Abstract: γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human ... ...

Abstract	γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary γδ T cells have been shown to kill in vitro DENV-infected cells, thus highlighting their possible antiviral function. The aim of this work was to characterize the phenotype and function of Vδ2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze Vδ2-T-cell frequency, differentiation profile, activation/exhaustion status, and functionality by multiparametric flow cytometry. Our data demonstrated that DENV infection was able to significantly reduce Vδ2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, Vδ2 T cells showed a reduced capability to produce IFN-γ after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of γδ-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of γδ T cells in the first phases of infection.
Keywords	dengue ; disease severity ; flow cytometry ; humans ; immunomodulation ; phenotype
Language	English
Dates of publication	2022-0112
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14010130
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Myeloid-Derived Suppressor Cells in COVID-19: The Paradox of Good.

Grassi, Germana / Notari, Stefania / Gili, Simona / Bordoni, Veronica / Casetti, Rita / Cimini, Eleonora / Tartaglia, Eleonora / Mariotti, Davide / Agrati, Chiara / Sacchi, Alessandra

Frontiers in immunology

2022 Volume 13, Page(s) 842949

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Viral replication in the respiratory tract induces the death of infected cells and the release of pathogen- associated molecular patterns (PAMPs). PAMPs give rise to local inflammation, increasing the secretion of pro- inflammatory cytokines and chemokines, which attract immune cells from the blood into the infected lung. In most individuals, lung-recruited cells clear the infection, and the immune response retreats. However, in some cases, a dysfunctional immune response occurs, which triggers a cytokine storm in the lung, leading to acute respiratory distress syndrome (ARDS). Severe COVID-19 is characterized by an impaired innate and adaptive immune response and by a massive expansion of myeloid-derived suppressor cells (MDSCs). MDSCs function as protective regulators of the immune response, protecting the host from over-immunoreactivity and hyper-inflammation. However, under certain conditions, such as chronic inflammation and cancer, MDSCs could exert a detrimental role. Accordingly, the early expansion of MDSCs in COVID-19 is able to predict the fatal outcome of the infection. Here, we review recent data on MDSCs during COVID-19, discussing how they can influence the course of the disease and whether they could be considered as biomarker and possible targets for new therapeutic approaches.
MeSH term(s)	COVID-19 ; Humans ; Inflammation ; Myeloid-Derived Suppressor Cells ; Pathogen-Associated Molecular Pattern Molecules ; SARS-CoV-2
Chemical Substances	Pathogen-Associated Molecular Pattern Molecules
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.842949
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Article ; Online: In Acute Dengue Infection, High TIM-3 Expression May Contribute to the Impairment of IFNγ Production by Circulating Vδ2 T Cells.

Cimini, Eleonora / Grassi, Germana / Beccacece, Alessia / Casetti, Rita / Castilletti, Concetta / Capobianchi, Maria Rosaria / Nicastri, Emanuele / Agrati, Chiara

Viruses

2022 Volume 14, Issue 1

Abstract	γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary γδ T cells have been shown to kill in vitro DENV-infected cells, thus highlighting their possible antiviral function. The aim of this work was to characterize the phenotype and function of Vδ2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze Vδ2-T-cell frequency, differentiation profile, activation/exhaustion status, and functionality by multiparametric flow cytometry. Our data demonstrated that DENV infection was able to significantly reduce Vδ2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, Vδ2 T cells showed a reduced capability to produce IFN-γ after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of γδ-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of γδ T cells in the first phases of infection.
MeSH term(s)	Adaptation, Physiological ; Adult ; Dengue/immunology ; Flow Cytometry ; Hepatitis A Virus Cellular Receptor 2/genetics ; Hepatitis A Virus Cellular Receptor 2/metabolism ; Humans ; Immunity, Innate ; Interferon-gamma/metabolism ; Intraepithelial Lymphocytes/immunology ; Leukocytes, Mononuclear/immunology ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; T-Lymphocyte Subsets/immunology
Chemical Substances	HAVCR2 protein, human ; Hepatitis A Virus Cellular Receptor 2 ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2022-01-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14010130
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Article ; Online: The interplay between SARS-CoV-2 infected airway epithelium and immune cells modulates regulatory/inflammatory signals.

Bordoni, Veronica / Matusali, Giulia / Mariotti, Davide / Antonioli, Manuela / Cimini, Eleonora / Sacchi, Alessandra / Tartaglia, Eleonora / Casetti, Rita / Grassi, Germana / Notari, Stefania / Castilletti, Concetta / Fimia, Gian Maria / Capobianchi, Maria Rosaria / Ippolito, Giuseppe / Agrati, Chiara

iScience

2022 Volume 25, Issue 2, Page(s) 103854

Abstract: To assess the cross-talk between immune cells and respiratory tract during SARS-CoV-2 infection, we analyzed the relationships between the inflammatory response induced by SARS-CoV-2 replication and immune cells phenotype in a reconstituted organotypic ... ...

Abstract	To assess the cross-talk between immune cells and respiratory tract during SARS-CoV-2 infection, we analyzed the relationships between the inflammatory response induced by SARS-CoV-2 replication and immune cells phenotype in a reconstituted organotypic human airway epithelium (HAE). The results indicated that immune cells failed to inhibit SARS-CoV-2 replication in the HAE model. In contrast, immune cells strongly affected the inflammatory profile induced by SARS-CoV-2 infection, dampening the production of several immunoregulatory/inflammatory signals (e.g., IL-35, IL-27, and IL-34). Moreover, these mediators were found inversely correlated with innate immune cell frequency (NK and γδ T cells) and directly with CD8 T cells. The enriched signals associated with NK and CD8 T cells highlighted the modulation of pathways induced by SARS-CoV-2 infected HAE. These findings are useful to depict the cell-cell communication mechanisms necessary to develop novel therapeutic strategies aimed to promote an effective immune response.
Language	English
Publishing date	2022-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103854
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Article ; Online: Myocarditis-associated necrotizing coronary vasculitis: incidence, cause, and outcome.

Frustaci, Andrea / Alfarano, Maria / Verardo, Romina / Agrati, Chiara / Casetti, Rita / Miraldi, Fabio / Galea, Nicola / Letizia, Claudio / Chimenti, Cristina

European heart journal

2020 Volume 42, Issue 16, Page(s) 1609–1617

Abstract: Aims: Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported.: Methods and results: Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. ... ...

Abstract	Aims: Necrotizing coronary vasculitis (NCV) is a rare entity usually associated to myocarditis which incidence, cause, and response to therapy is unreported. Methods and results: Among 1916 patients with biopsy-proven myocarditis, 30 had NCV. Endomyocardial samples were retrospectively investigated with immunohistochemistry for toll-like receptor 4 (TLR4) and real-time polymerase chain reaction (PCR) for viral genomes. Serum samples were processed for anti-heart autoantibodies (Abs), IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α. Identification of an immunologic pathway (including virus-negativity, TLR4-, and Ab-positivity) was followed by immunosuppression. Myocarditis-NCV cohort was followed for 6 months with 2D-echo and/or cardiac magnetic resonance and compared with 60 Myocarditis patients and 30 controls. Increase in left ventricular ejection fraction ≥10% was classified as response to therapy. Control endomyocardial biopsy followed the end of treatment. Twenty-six Myocarditis-NCV patients presented with heart failure; four with electrical instability. Cause of Myocarditis-NCV included infectious agents (10%) and immune-mediated causes (chest trauma 3%; drug hypersensitivity 7%; hypereosinophilic syndrome 3%; primary autoimmune diseases 33%, idiopathic 44%). Abs were positive in immune-mediated Myocarditis-NCV and virus-negative Myocarditis; Myocarditis-NCV patients with Ab+ presented autoreactivity in vessel walls. Toll-like receptor 4 was overexpressed in immune-mediated forms and poorly detectable in viral. Interleukin-1β was significantly higher in Myocarditis-NCV than Myocarditis, the former presenting 24% in-hospital mortality compared with 1.5% of Myocarditis cohort. Immunosuppression induced improvement of cardiac function in 88% of Myocarditis-NCV and 86% of virus-negative Myocarditis patients. Conclusion: Necrotizing coronary vasculitis is histologically detectable in 1.5% of Myocarditis. Necrotizing coronary vasculitis includes viral and immune-mediated causes. Intra-hospital mortality is 24%. The immunologic pathway is associated with beneficial response to immunosuppression.
MeSH term(s)	Biopsy ; Humans ; Incidence ; Myocarditis/epidemiology ; Myocarditis/etiology ; Myocardium ; Retrospective Studies ; Stroke Volume ; Vasculitis/epidemiology ; Vasculitis/etiology ; Ventricular Function, Left
Language	English
Publishing date	2020-12-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehaa973
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Expansion of Myeloid Derived Suppressor Cells Contributes to Platelet Activation by L-Arginine Deprivation during SARS-CoV-2 Infection.

Sacchi, Alessandra / Grassi, Germana / Notari, Stefania / Gili, Simona / Bordoni, Veronica / Tartaglia, Eleonora / Casetti, Rita / Cimini, Eleonora / Mariotti, Davide / Garotto, Gabriele / Beccacece, Alessia / Marchioni, Luisa / Bibas, Michele / Nicastri, Emanuele / Ippolito, Giuseppe / Agrati, Chiara

Cells

2021 Volume 10, Issue 8

Abstract: Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID- ... ...

Abstract	Massive platelet activation and thrombotic events characterize severe COVID-19, highlighting their critical role in SARS-CoV-2-induced immunopathology. Since there is a well-described expansion of myeloid-derived suppressor cells (MDSC) in severe COVID-19, we evaluated their possible role in platelet activation during SARS-CoV-2 infection. During COVID-19, a lower plasmatic L-arginine level was observed compared to healthy donors, which correlated with MDSC frequency. Additionally, activated GPIIb/IIIa complex (PAC-1) expression was higher on platelets from severe COVID-19 patients compared to healthy controls and inversely correlated with L-arginine plasmatic concentration. Notably, MDSC were able to induce PAC-1 expression in vitro by reducing L-arginine concentration, indicating a direct role of PMN-MDSC in platelet activation. Accordingly, we found a positive correlation between ex vivo platelet PAC-1 expression and PMN-MDSC frequency. Overall, our data demonstrate the involvement of PMN-MDSC in triggering platelet activation during COVID-19, highlighting a novel role of MDSC in driving COVID-19 pathogenesis.
Language	English
Publishing date	2021-08-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10082111
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Article ; Online: High Levels of TRIM5α Are Associated with Xenophagy in HIV-1-Infected Long-Term Nonprogressors.

Ciccosanti, Fabiola / Corazzari, Marco / Casetti, Rita / Amendola, Alessandra / Collalto, Diletta / Refolo, Giulia / Vergori, Alessandra / Taibi, Chiara / D'Offizi, Gianpiero / Antinori, Andrea / Agrati, Chiara / Fimia, Gian Maria / Ippolito, Giuseppe / Piacentini, Mauro / Nardacci, Roberta

Cells

2021 Volume 10, Issue 5

Abstract: Autophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a ... ...

Abstract	Autophagy is a lysosomal-dependent degradative mechanism essential in maintaining cellular homeostasis, but it is also considered an ancient form of innate eukaryotic fighting against invading microorganisms. Mounting evidence has shown that HIV-1 is a critical target of autophagy that plays a role in HIV-1 replication and disease progression. In a special subset of HIV-1-infected patients that spontaneously and durably maintain extremely low viral replication, namely, long-term nonprogressors (LTNP), the resistance to HIV-1-induced pathogenesis is accompanied, in vivo, by a significant increase in the autophagic activity in peripheral blood mononuclear cells. Recently, a new player in the battle of autophagy against HIV-1 has been identified, namely, tripartite motif protein 5α (TRIM5α). In vitro data demonstrated that TRIM5α directly recognizes HIV-1 and targets it for autophagic destruction, thus protecting cells against HIV-1 infection. In this paper, we analyzed the involvement of this factor in the control of HIV-1 infection through autophagy, in vivo, in LTNP. The results obtained showed significantly higher levels of TRIM5α expression in cells from LTNP with respect to HIV-1-infected normal progressor patients. Interestingly, the colocalization of TRIM5α and HIV-1 proteins in autophagic vacuoles in LTNP cells suggested the participation of TRIM5α in the autophagy containment of HIV-1 in LTNP. Altogether, our results point to a protective role of TRIM5α in the successful control of the chronic viral infection in HIV-1-controllers through the autophagy mechanism. In our opinion, these findings could be relevant in fighting against HIV-1 disease, because autophagy inducers might be employed in combination with antiretroviral drugs.
MeSH term(s)	Adult ; Aged ; Autophagy ; Case-Control Studies ; Cohort Studies ; Female ; HIV Infections/immunology ; HIV Long-Term Survivors ; HIV-1 ; Humans ; Male ; Middle Aged ; Tripartite Motif Proteins/immunology ; Ubiquitin-Protein Ligases/immunology ; Virus Replication ; Young Adult
Chemical Substances	Tripartite Motif Proteins ; TRIM5 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-05-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10051207
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Article ; Online: Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV.

Pinnetti, Carmela / Cimini, Eleonora / Vergori, Alessandra / Mazzotta, Valentina / Grassi, Germana / Mondi, Annalisa / Forbici, Federica / Amendola, Alessandra / Grisetti, Susanna / Baldini, Francesco / Candela, Caterina / Casetti, Rita / Campioni, Paolo / Capobianchi, Maria Rosaria / Agrati, Chiara / Antinori, Andrea

Viruses

2022 Volume 14, Issue 5

Abstract: Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell ... ...

Abstract	Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29-52), median CD4 and CD8 count 150 (15-158) and 973 (354-1250) cell/mm
MeSH term(s)	Adult ; Antibodies, Monoclonal, Humanized/therapeutic use ; DNA, Viral/genetics ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal/drug therapy ; Leukoencephalopathy, Progressive Multifocal/virology ; Male ; Middle Aged ; Polyomavirus Infections/complications ; Polyomavirus Infections/drug therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; RNA, Viral ; Virus Activation
Chemical Substances	Antibodies, Monoclonal, Humanized ; DNA, Viral ; Programmed Cell Death 1 Receptor ; RNA, Viral ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2022-05-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14050970
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Article ; Online: Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study.

Mazzotta, Valentina / Lepri, Alessandro Cozzi / Matusali, Giulia / Cimini, Eleonora / Piselli, Pierluca / Aguglia, Camilla / Lanini, Simone / Colavita, Francesca / Notari, Stefania / Oliva, Alessandra / Meschi, Silvia / Casetti, Rita / Mondillo, Vanessa / Vergori, Alessandra / Bettini, Aurora / Grassi, Germana / Pinnetti, Carmela / Lapa, Daniele / Tartaglia, Eleonora /

Gallì, Paola / Mondi, Annalisa / Montagnari, Giulia / Gagliardini, Roberta / Nicastri, Emanuele / Lichtner, Miriam / Sarmati, Loredana / Tamburrini, Enrica / Mastroianni, Claudio / Stingone, Christof / Siddu, Andrea / Barca, Alessandra / Fontana, Carla / Agrati, Chiara / Girardi, Enrico / Vaia, Francesco / Maggi, Fabrizio / Antinori, Andrea

EClinicalMedicine

2024 Volume 68, Page(s) 102420

Abstract: Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve ... ...

Abstract	Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5 × 1000, 2021" and by the Italian Ministry of Health "
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2023.102420
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