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  1. Article ; Online: Therapeutic potential of convalescent plasma and hyperimmune immunoglobulins against SARS-CoV-2 BQ.1, BQ.1.1, and XBB variants

    Lorenza Bellusci / Hana Golding / Surender Khurana

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 8

    Keywords COVID-19 ; Therapeutics ; Medicine ; R
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Immune Response to SARS-CoV-2 Vaccine and Following Breakthrough Omicron Infection in an Autoimmune Patient with Hashimoto’s Thyroiditis, Pernicious Anemia, and Chronic Atrophic Autoimmune Gastritis

    Emily Cluff / Lorenza Bellusci / Hana Golding / Surender Khurana

    Vaccines, Vol 10, Iss 450, p

    A Case Report

    2022  Volume 450

    Abstract: In healthy adults, hybrid immunity induced by prior SARS-CoV-2 infection followed by two doses of mRNA vaccination provide protection against symptomatic SARS-CoV-2 infection. However, the role of hybrid immunity in autoimmune patients against Omicron is ...

    Abstract In healthy adults, hybrid immunity induced by prior SARS-CoV-2 infection followed by two doses of mRNA vaccination provide protection against symptomatic SARS-CoV-2 infection. However, the role of hybrid immunity in autoimmune patients against Omicron is not well documented. Here, we report a young autoimmune patient with prior infection and two doses of mRNA-1273 vaccination who was exposed to Omicron and developed a symptomatic disease. Prior to Omicron infection, the patient had strong neutralizing antibody titers against the vaccine strain, but no neutralization of Omicron. Post Omicron infection, high neutralizing titers against Omicron were observed. Furthermore, enhanced neutralizing antibody titers against other variants of concern—Alpha, Beta, Gamma, and Delta—were observed, suggesting an expansion of cross-reactive memory B-cell response by the SARS-CoV-2 Omicron infection. Autoimmune patients may require careful monitoring of immune function over time to optimize booster vaccine administration.
    Keywords COVID-19 ; Omicron ; SARS-CoV-2 ; neutralization ; autoimmune ; Hashimoto’s ; Medicine ; R
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Protective antigenic sites identified in respiratory syncytial virus fusion protein reveals importance of p27 domain

    Jeehyun Lee / Youri Lee / Laura Klenow / Elizabeth M Coyle / Juanjie Tang / Supriya Ravichandran / Hana Golding / Surender Khurana

    EMBO Molecular Medicine, Vol 14, Iss 1, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Respiratory syncytial virus (RSV) vaccines primarily focused on surface fusion (F) protein are under development. Therefore, to identify RSV‐F protective epitopes, we evaluated 14 antigenic sites recognized following primary human RSV infection. ...

    Abstract Abstract Respiratory syncytial virus (RSV) vaccines primarily focused on surface fusion (F) protein are under development. Therefore, to identify RSV‐F protective epitopes, we evaluated 14 antigenic sites recognized following primary human RSV infection. BALB/c mice were vaccinated with F peptides, F proteins, or RSV‐A2, followed by rA2‐Line19F challenge. F peptides generated binding antibodies with minimal in vitro neutralization titers. However, several F peptides (including Site II) reduced lung viral loads and lung pathology scores in animals, suggesting partial protection from RSV disease. Interestingly, animals vaccinated with peptides (aa 101–121 and 110–136) spanning the F‐p27 sequence, which is only present in unprocessed F0 protein, showed control of viral loads with significantly reduced pathology compared with mock‐vaccinated controls. Furthermore, we observed F‐p27 expression on the surface of RSV‐infected cells as well as lungs from RSV‐infected mice. The anti‐p27 antibodies demonstrated antibody‐dependent cellular cytotoxicity (ADCC) of RSV‐infected A549 cells. These findings suggest that p27‐mediated immune response may play a role in control of RSV disease in vivo, and F‐p27 should be considered for inclusion in an effective RSV vaccine.
    Keywords epitope ; F protein ; neutralization ; RSV ; vaccine ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Antibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination

    Lorenza Bellusci / Gabrielle Grubbs / Fatema Tuz Zahra / David Forgacs / Hana Golding / Ted M. Ross / Surender Khurana

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Here the authors show that a third SARS-CoV-2 vaccination significantly boosts neutralizing antibodies against Omicron subvariants and that hybrid immunity (infection and vaccination) results in broader neutralization activity and cross-reactive antibody ...

    Abstract Here the authors show that a third SARS-CoV-2 vaccination significantly boosts neutralizing antibodies against Omicron subvariants and that hybrid immunity (infection and vaccination) results in broader neutralization activity and cross-reactive antibody affinity maturation.
    Keywords Science ; Q
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: D-dimer and CoV-2 spike-immune complexes contribute to the production of PGE2 and proinflammatory cytokines in monocytes.

    Yun-Jong Park / David Acosta / Russell Vassell / Juanjie Tang / Surender Khurana / Carol D Weiss / Hana Golding / Marina Zaitseva

    PLoS Pathogens, Vol 18, Iss 4, p e

    2022  Volume 1010468

    Abstract: An overreactive inflammatory response and coagulopathy are observed in patients with severe form of COVID-19. Since increased levels of D-dimer (DD) are associated with coagulopathy in COVID-19, we explored whether DD contributes to the aberrant cytokine ...

    Abstract An overreactive inflammatory response and coagulopathy are observed in patients with severe form of COVID-19. Since increased levels of D-dimer (DD) are associated with coagulopathy in COVID-19, we explored whether DD contributes to the aberrant cytokine responses. Here we show that treatment of healthy human monocytes with DD induced a dose dependent increase in production of pyrogenic mediator, Prostaglandin E2 (PGE2) and inflammatory cytokines, IL-6 and IL-8. The DD-induced PGE2 and inflammatory cytokines were enhanced significantly by co-treatment with immune complexes (IC) of SARS CoV-2 recombinant S protein or of pseudovirus containing SARS CoV-2 S protein (PVCoV-2) coated with spike-specific chimeric monoclonal antibody (MAb) containing mouse variable and human Fc regions. The production of PGE2 and cytokines in monocytes activated with DD and ICs was sensitive to the inhibitors of β2 integrin and FcγRIIa, and to the inhibitors of calcium signaling, Mitogen-Activated Protein Kinase (MAPK) pathway, and tyrosine-protein kinase. Importantly, strong increase in PGE2 and in IL-6/IL-8/IL-1β cytokines was observed in monocytes activated with DD in the presence of IC of PVCoV-2 coated with plasma from hospitalized COVID-19 patients but not from healthy donors. The IC of PVCoV-2 with convalescent plasma induced much lower levels of PGE2 and cytokines compared with plasma from hospitalized COVID-19 patients. PGE2 and IL-6/IL-8 cytokines produced in monocytes activated with plasma-containing IC, correlated well with the levels of spike binding antibodies and not with neutralizing antibody titers. Our study suggests that a combination of high levels of DD and high titers of spike-binding antibodies that can form IC with SARS CoV-2 viral particles might accelerate the inflammatory status of lung infiltrating monocytes leading to increased lung pathology in patients with severe form of COVID-19.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Antibody affinity maturation and cross-variant activity following SARS-CoV-2 mRNA vaccination

    Juanjie Tang / Gabrielle Grubbs / Youri Lee / Chang Huang / Supriya Ravichandran / David Forgacs / Hana Golding / Ted M Ross / Surender Khurana

    EBioMedicine, Vol 74, Iss , Pp 103748- (2021)

    Impact of prior exposure and sex

    2021  

    Abstract: Background: Limited knowledge exists regarding antibody affinity maturation following mRNA vaccination in naïve vs. COVID-19 recovered individuals and potential sex differences. Methods: We elucidated post-vaccination antibody profiles of 69 naïve and 17 ...

    Abstract Background: Limited knowledge exists regarding antibody affinity maturation following mRNA vaccination in naïve vs. COVID-19 recovered individuals and potential sex differences. Methods: We elucidated post-vaccination antibody profiles of 69 naïve and 17 COVID-19 convalescent adults using pseudovirus neutralization assay (PsVNA) covering SARS-CoV-2 WA-1, variants of concern (VOCs) and variants of interest (VOIs). Surface Plasmon Resonance (SPR) was used to measure antibody affinity against prefusion spike and receptor binding domain (RBD) and RBD mutants. Findings: Higher neutralizing antibodies were observed in convalescent vs. naïve adults against, WA-1, VOCs, and VOIs. Antibody binding to RBD and RBD mutants showed lower binding of post-vaccination sera from naïve compared with convalescent individuals. Moreover, we observed early antibody affinity maturation in convalescent individuals after one vaccine dose and higher antibody affinity after two doses compared with the naïve group. Among the naïve participants, antibody affinity against the SARS-CoV-2 prefusion spike was significantly higher for males than females even though there were no difference in neutralization titers between sexes. Interpretation: This study demonstrates the impact of prior infection on vaccine-induced antibody affinity maturation and difference in antibody affinity between males and females. Further studies are needed to determine whether antibody affinity may contribute to correlates of protection against SARS-CoV-2 and its variants. Funding: The antibody characterization work described in this manuscript was supported by FDA's Medical Countermeasures Initiative (MCMi) grant #OCET 2021-1565 to S.K and intramural FDA-CBER COVID-19 supplemental funds. The SPARTA program was supported by the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH), Department of Health and Human Services contract 75N93019C00052, and the University of Georgia (US) grant UGA-001. T.M.R is also supported by ...
    Keywords SARS-CoV-2 ; COVID-19 ; Vaccine ; Virus neutralization ; Affinity maturation ; Sex differences ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Antibody affinity maturation and plasma IgA associate with clinical outcome in hospitalized COVID-19 patients

    Juanjie Tang / Supriya Ravichandran / Youri Lee / Gabrielle Grubbs / Elizabeth M. Coyle / Laura Klenow / Hollie Genser / Hana Golding / Surender Khurana

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: SARS-CoV2 infection has been linked to a wide range of clinical severities and the immunopathology is still under intense scrutiny. Here, the authors uncover an association of antibody affinity maturation and plasma IgA levels with clinical outcome in ... ...

    Abstract SARS-CoV2 infection has been linked to a wide range of clinical severities and the immunopathology is still under intense scrutiny. Here, the authors uncover an association of antibody affinity maturation and plasma IgA levels with clinical outcome in patients with COVID-19 disease.
    Keywords Science ; Q
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Protective antigenic sites in respiratory syncytial virus G attachment protein outside the central conserved and cysteine noose domains.

    Jeehyun Lee / Laura Klenow / Elizabeth M Coyle / Hana Golding / Surender Khurana

    PLoS Pathogens, Vol 14, Iss 8, p e

    2018  Volume 1007262

    Abstract: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. Previously, we elucidated the antibody repertoire following primary RSV infection in infants. Whole genome-fragment phage display libraries (GFPDL) ... ...

    Abstract Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract disease in infants. Previously, we elucidated the antibody repertoire following primary RSV infection in infants. Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational epitopes from RSV bound 100-fold more phages within attachment protein (G) following primary RSV infection. The G-reactive epitopes spanned the N- and C-termini of G ectodomain, in addition to the central conserved domain (CCD). In the current study, we examined the contribution of antigenic regions of G outside of the CCD to RSV-specific immunity. We evaluated the immunogenicity, neutralization and protective efficacy of all RSV-G antigenic sites identified following primary RSV infection using recombinant E. coli expressed G ectodomain (REG), CCD-deleted G ectodomain (REG ΔCCD), N- and C-terminal G subdomains, and antigenic site peptides. The REG ΔCCD, N- and C-terminal subdomains and peptides generated antibody titers in rabbits and mice that bound fully glycosylated Recombinant Mammalian expressed G ectodomain (RMG) and intact RSV virion particles but minimal in vitro neutralization titers compared with the intact G ectodomain. Vaccinated mice were challenged intranasally with RSV-A2 Line 19F. Viral replication in nasal cavity and lungs was significantly reduced in vaccinated animals compared to unimmunized controls. Control of viral loads post-RSV challenge correlated with serum antibody binding to the virus particles. In addition, very low Th2/Th1 cytokine ratios were found in the lungs of REG ΔCCD vaccinated mice after challenge. These data demonstrate the presence of multiple protective sites in RSV G protein outside of the CCD that could contribute to the development of a bacterially produced unglycosylated G protein as safe and protective vaccine against RSV disease.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2018-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans

    Surender Khurana / Megan Hahn / Elizabeth M. Coyle / Lisa R. King / Tsai-Lien Lin / John Treanor / Andrea Sant / Hana Golding

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine ... ...

    Abstract Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.
    Keywords Science ; Q
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Portfolio
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    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans

    Surender Khurana / Megan Hahn / Elizabeth M. Coyle / Lisa R. King / Tsai-Lien Lin / John Treanor / Andrea Sant / Hana Golding

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine ... ...

    Abstract Here, Khurana et al. report the results of a phase 4 clinical trial with three FDA approved influenza vaccines and show that repeat influenza vaccination results in reduced antibody affinity maturation to hemagglutinin domain 1 irrespective of vaccine platform.
    Keywords Science ; Q
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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