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Article ; Online: SARS-CoV-2 Hybrid Immunity: The Best of Both Worlds.

Lasrado, Ninaad / Barouch, Dan H

2023 Volume 228, Issue 10, Page(s) 1311–1313

Abstract: Three and a half years into the coronavirus disease 2019 (COVID-19) pandemic, the nature and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still remains unclear. Current COVID-19 mRNA vaccines have been ... ...

Abstract	Three and a half years into the coronavirus disease 2019 (COVID-19) pandemic, the nature and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still remains unclear. Current COVID-19 mRNA vaccines have been shown to provide minimal protection against infection with XBB variants but substantial protection against severe disease. However, such protection appears to wane quickly. In contrast, protection from the combination of both vaccination and infection, termed "hybrid immunity", has been shown to be greater in magnitude and durability than that provided by either vaccine immunity or natural immunity alone.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; COVID-19 Vaccines ; Immunity, Innate ; Vaccination ; Adaptive Immunity ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad353
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Article: Vaccines against Group B Coxsackieviruses and Their Importance.

Mone, Kiruthiga / Lasrado, Ninaad / Sur, Meghna / Reddy, Jay

Vaccines

2023 Volume 11, Issue 2

Abstract: The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the ... ...

Abstract	The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.
Language	English
Publishing date	2023-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11020274
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Article ; Online: Neutralization of SARS-CoV-2 Omicron subvariant BA.2.87.1.

Lasrado, Ninaad / Rössler, Annika / Rowe, Marjorie / Collier, Ai-Ris Y / Barouch, Dan H

Vaccine

2024 Volume 42, Issue 9, Page(s) 2117–2121

Abstract: A new highly mutated Omicron subvariant BA.2.87.1 has recently been identified with over 30 amino acid mutations in the Spike protein compared with BA.2, BA.5, XBB.1.5, and JN.1 variants. Mutiple mutations in BA.2.87.1 are located in the N-terminal ... ...

Abstract	A new highly mutated Omicron subvariant BA.2.87.1 has recently been identified with over 30 amino acid mutations in the Spike protein compared with BA.2, BA.5, XBB.1.5, and JN.1 variants. Mutiple mutations in BA.2.87.1 are located in the N-terminal domain (NTD) rather than in the receptor binding domain (RBD) of the Spike protein. We evaluated neutralizing antibody (NAb) responses to BA.2.87.1 because of its highly mutated sequence and its unique NTD region. Our data show that NAb responses to BA.2.87.1 were lower than to BA.2 but higher than to JN.1, suggesting that BA.2.87.1 is not a further antibody escape variant compared with other currently circulating variants. Moreover, XBB.1.5 mRNA boosting increased NAb titers to all variants tested including BA.2.87.1.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Amino Acids ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	Spike Glycoprotein, Coronavirus ; Amino Acids ; Antibodies, Neutralizing ; Antibodies, Viral ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-03-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2024.03.007
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Article ; Online: An overview of the immune mechanisms of viral myocarditis.

Lasrado, Ninaad / Reddy, Jay

Reviews in medical virology

2020 Volume 30, Issue 6, Page(s) 1–14

Abstract: Viral myocarditis has been identified as a major cause of dilated cardiomyopathy (DCM) that can lead to heart failure. Historically, Coxsackieviruses and adenoviruses have been commonly suspected in myocarditis/DCM patients in North America and Europe. ... ...

Abstract	Viral myocarditis has been identified as a major cause of dilated cardiomyopathy (DCM) that can lead to heart failure. Historically, Coxsackieviruses and adenoviruses have been commonly suspected in myocarditis/DCM patients in North America and Europe. However, this notion is changing as other viruses such as Parvovirus B19 and human herpesvirus-6 are increasingly reported as causes of myocarditis in the United States, with the most recent example being the severe acute respiratory syndrome coronavirus 2, causing the Coronavirus Disease-19. The mouse model of Coxsackievirus B3 (CVB3)-induced myocarditis, which may involve mediation of autoimmunity, is routinely used in the study of immune pathogenesis of viral infections as triggers of DCM. In this review, we discuss the immune mechanisms underlying the development of viral myocarditis with an emphasis on autoimmunity in the development of post-infectious myocarditis induced with CVB3.
MeSH term(s)	Adaptive Immunity ; Animals ; Autoimmunity ; Biomarkers ; Cytokines/metabolism ; Disease Models, Animal ; Disease Progression ; Disease Susceptibility/immunology ; Gene Expression Regulation ; Gene Knockdown Techniques ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Inflammation Mediators/metabolism ; Mice ; Myocarditis/immunology ; Myocarditis/pathology ; Myocarditis/virology ; Signal Transduction
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators
Keywords	covid19
Language	English
Publishing date	2020-07-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1086043-5
ISSN	1099-1654 ; 1052-9276
ISSN (online)	1099-1654
ISSN	1052-9276
DOI	10.1002/rmv.2131
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Investigation into Cardiac Myhc-α 334-352-Specific TCR Transgenic Mice Reveals a Role for Cytotoxic CD4 T Cells in the Development of Cardiac Autoimmunity.

Sur, Meghna / Rasquinha, Mahima T / Mone, Kiruthiga / Massilamany, Chandirasegaran / Lasrado, Ninaad / Gurumurthy, Channabasavaiah / Sobel, Raymond A / Reddy, Jay

Cells

2024 Volume 13, Issue 3

Abstract: Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive ... ...

Abstract	Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4
MeSH term(s)	Animals ; Humans ; Mice ; Autoimmunity ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes/pathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Myocarditis ; Myosin Heavy Chains/genetics ; Receptors, Antigen, T-Cell ; T-Lymphocytes, Cytotoxic
Chemical Substances	Myh6 protein, mouse ; Myosin Heavy Chains (EC 3.6.4.1) ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13030234
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Article: Mt10 Vaccine Protects Diversity Outbred Mice from CVB3 Infection by Producing Virus-Specific Neutralizing Antibodies and Diverse Antibody Isotypes.

Rasquinha, Mahima T / Mone, Kiruthiga / Sur, Meghna / Lasrado, Ninaad / Massilamany, Chandirasegaran / Kachman, Stephen D / Steffen, David / Reddy, Jay

Vaccines

2024 Volume 12, Issue 3

Abstract: Group B coxsackieviruses (CVBs) cause a wide range of diseases in humans, but no vaccines are currently available to prevent these infections. Previously, we had demonstrated that a live attenuated CVB3 vaccine virus, Mutant 10 (Mt10), offers protection ... ...

Abstract	Group B coxsackieviruses (CVBs) cause a wide range of diseases in humans, but no vaccines are currently available to prevent these infections. Previously, we had demonstrated that a live attenuated CVB3 vaccine virus, Mutant 10 (Mt10), offers protection against multiple CVB serotypes as evaluated in various inbred mouse strains; however, the applicability of these findings to the outbred human population remains uncertain. To address this issue, we used Diversity Outbred (DO) mice, whose genome is derived from eight inbred mouse strains that may capture the level of genetic diversity of the outbred human population. To determine the efficacy of the Mt10 vaccine, we established the CVB3 infection model in the DO mice. We noted that CVB3 infection resulted mainly in pancreatitis, although viral RNA was detected in both the pancreas and heart. Histologically, the pancreatic lesions comprised of necrosis, post-necrotic atrophy, and lymphocyte infiltration. In evaluating the efficacy of the Mt10 vaccine, both male and female DO mice were completely protected in challenge studies with CVB3, and viral RNA was not detected in the heart or pancreas. Likewise, vaccine recipients of both sexes showed significant levels of virus-neutralizing antibodies. Furthermore, by using the CVB3 viral protein 1, virus-reactive antibodies were found to be diverse in the order of IgG2c, followed by IgG2a, IgG2b/IgG3, and IgG1. Together, the data suggest that the Mt10 vaccine virus can offer protection against CVB infections that may have translational significance.
Language	English
Publishing date	2024-03-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12030266
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Article: Triggers of Inflammatory Heart Disease.

Lasrado, Ninaad / Yalaka, Bharathi / Reddy, Jay

Frontiers in cell and developmental biology

2020 Volume 8, Page(s) 192

Abstract: Inflammatory heart disease (IHD) is a group of diseases that includes pericarditis, myocarditis, and endocarditis. Although males appear to be more commonly affected than females, IHD can be seen in any age group. While the disease can be self-limiting ... ...

Abstract	Inflammatory heart disease (IHD) is a group of diseases that includes pericarditis, myocarditis, and endocarditis. Although males appear to be more commonly affected than females, IHD can be seen in any age group. While the disease can be self-limiting leading to full recovery, affected individuals can develop chronic disease, suggesting that identification of primary triggers is critical for successful therapies. Adding to this complexity, however, is the fact that IHD can be triggered by a variety of infectious and non-infectious causes that can also occur as secondary events to primary insults. In this review, we discuss the immunological insights into the development of IHD as well as a mechanistic understanding of the disease process in animal models.
Language	English
Publishing date	2020-03-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2020.00192
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: IL-10 as a Th2 Cytokine: Differences Between Mice and Humans.

Rasquinha, Mahima T / Sur, Meghna / Lasrado, Ninaad / Reddy, Jay

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 207, Issue 9, Page(s) 2205–2215

Abstract: The discovery of IL-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between Th1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its ... ...

Abstract	The discovery of IL-10 more than 30 years ago marked the beginning of our understanding of how cytokines regulate immune responses, based on cross-regulation between Th1 and Th2 cytokines. Although multiple cell types were shown to produce IL-10, its identity as a Th2 cytokine remained strong because it was rigidly associated with Th2 clones in mice, whereas both Th1 and Th2 clones could secrete IL-10 in humans. However, as new Th1/Th2 cell functionalities emerged, anti-inflammatory action of IL-10 gained more attention than its inhibitory effect on Th1 cells, which may occur as an indirect consequence of suppression of APCs. This notion is also supported by the discovery of regulatory T cells, whose suppressor functions involve the mediation of IL-10, among other molecules. From this perspective, we discuss the functionalities of IL-10 by highlighting important differences between mice and humans with an emphasis on the Th1 and Th2 paradigm.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Immune Tolerance ; Interleukin-10/metabolism ; Mice ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology ; Th1-Th2 Balance ; Th2 Cells/immunology
Chemical Substances	Interleukin-10 (130068-27-8)
Language	English
Publishing date	2021-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100565
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Article ; Online: Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing.

Lasrado, Ninaad / Borcherding, Nicholas / Arumugam, Rajkumar / Starr, Timothy K / Reddy, Jay

iScience

2022 Volume 25, Issue 3, Page(s) 103865

Abstract: Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice. Chronically affected mice may develop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, ...

Abstract	Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice. Chronically affected mice may develop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells from healthy and myocarditic mice, leading us to note significant proportions of myeloid cells, T cells, and fibroblasts. Although the transcriptomes of myeloid cells were mainly of M2 phenotype, the Th17 cells, CTLs, and Treg cells had signatures critical for cytotoxic functions. Fibroblasts were heterogeneous expressing genes important in fibrosis and regulation of inflammation and immune responses. The intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells had upregulated unique transcription factors modulating cardiac remodeling functions. Together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103865
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: An overview of the immune mechanisms of viral myocarditis

Lasrado, Ninaad / Reddy, Jay

Rev Med Virol

Abstract	Viral myocarditis has been identified as a major cause of dilated cardiomyopathy (DCM) that can lead to heart failure. Historically, Coxsackieviruses and adenoviruses have been commonly suspected in myocarditis/DCM patients in North America and Europe. However, this notion is changing as other viruses such as Parvovirus B19 and human herpesvirus-6 are increasingly reported as causes of myocarditis in the United States, with the most recent example being the severe acute respiratory syndrome coronavirus 2, causing the Coronavirus Disease-19. The mouse model of Coxsackievirus B3 (CVB3)-induced myocarditis, which may involve mediation of autoimmunity, is routinely used in the study of immune pathogenesis of viral infections as triggers of DCM. In this review, we discuss the immune mechanisms underlying the development of viral myocarditis with an emphasis on autoimmunity in the development of post-infectious myocarditis induced with CVB3.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #680696
Database	COVID19

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