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Article ; Online: Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.

Sankhala, Rajeshwer S / Lal, Kerri G / Jensen, Jaime L / Dussupt, Vincent / Mendez-Rivera, Letzibeth / Bai, Hongjun / Wieczorek, Lindsay / Mayer, Sandra V / Zemil, Michelle / Wagner, Danielle A / Townsley, Samantha M / Hajduczki, Agnes / Chang, William C / Chen, Wei-Hung / Donofrio, Gina C / Jian, Ningbo / King, Hannah A D / Lorang, Cynthia G / Martinez, Elizabeth J /

Rees, Phyllis A / Peterson, Caroline E / Schmidt, Fabian / Hart, Tricia J / Duso, Debra K / Kummer, Lawrence W / Casey, Sean P / Williams, Jazmean K / Kannan, Shruthi / Slike, Bonnie M / Smith, Lauren / Swafford, Isabella / Thomas, Paul V / Tran, Ursula / Currier, Jeffrey R / Bolton, Diane L / Davidson, Edgar / Doranz, Benjamin J / Hatziioannou, Theodora / Bieniasz, Paul D / Paquin-Proulx, Dominic / Reiley, William W / Rolland, Morgane / Sullivan, Nancy J / Vasan, Sandhya / Collins, Natalie D / Modjarrad, Kayvon / Gromowski, Gregory D / Polonis, Victoria R / Michael, Nelson L / Krebs, Shelly J / Joyce, M Gordon

Nature communications

2024 Volume 15, Issue 1, Page(s) 200

Abstract: The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody ... ...

Abstract	The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.
MeSH term(s)	Animals ; Mice ; Antibodies, Neutralizing ; Macaca mulatta ; Vaccination ; Antibodies, Viral ; Antibodies, Monoclonal ; COVID-19 Vaccines ; Ferritins ; Nanoparticles ; Severe acute respiratory syndrome-related coronavirus ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Antibodies, Monoclonal ; COVID-19 Vaccines ; Ferritins (9007-73-2) ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44265-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

Garrido, Carolina / Hurst, Jillian H / Lorang, Cynthia G / Aquino, Jhoanna N / Rodriguez, Javier / Pfeiffer, Trevor S / Singh, Tulika / Semmes, Eleanor C / Lugo, Debra J / Rotta, Alexandre T / Turner, Nicholas A / Burke, Thomas W / McClain, Micah T / Petzold, Elizabeth A / Permar, Sallie R / Moody, M Anthony / Woods, Christopher W / Kelly, Matthew S / Fouda, Genevieve G

JCI insight

2021 Volume 6, Issue 17

Abstract: As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or ...

Abstract	As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus-neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate that children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that can likely contribute to protection from reinfection.
MeSH term(s)	Adolescent ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Asymptomatic Diseases ; COVID-19/blood ; COVID-19/immunology ; COVID-19/pathology ; Child ; Female ; Humans ; Male ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2021-09-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.150909
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents.

medRxiv : the preprint server for health sciences

2021

Abstract	As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.04.17.21255663
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

Garrido, Carolina / Hurst, Jillian H / Lorang, Cynthia G. / Aquino, Jhoanna N. / Rodriguez, Javier / Pfeiffer, Trevor S. / Singh, Tulika / Semmes, Eleanor C. / Lugo, Debra J. / Rotta, Alexandre T. / Turner, Nicholas A. / Burke, Thomas W. / McClain, Micah T / Petzold, Elizabeth A. / Permar, Sallie R. / Moody, M. Anthony / Woods, Christopher W. / Kelly, Matthew S / Fouda, Genevieve G.

medRxiv

Abstract	As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.
Keywords	covid19
Language	English
Publishing date	2021-04-20
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.04.17.21255663
Database	COVID19

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Article: Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.

Lima, Noemia S / Musayev, Maryam / Johnston, Timothy S / Wagner, Danielle A / Henry, Amy R / Wang, Lingshu / Yang, Eun Sung / Zhang, Yi / Birungi, Kevina / Black, Walker P / O'Dell, Sijy / Schmidt, Stephen D / Moon, Damee / Lorang, Cynthia G / Zhao, Bingchun / Chen, Man / Boswell, Kristin L / Roberts-Torres, Jesmine / Davis, Rachel L /

Peyton, Lowrey / Narpala, Sandeep R / O'Connell, Sarah / Wang, Jennifer / Schrager, Alexander / Talana, Chloe Adrienna / Leung, Kwanyee / Shi, Wei / Khashab, Rawan / Biber, Asaf / Zilberman, Tal / Rhein, Joshua / Vetter, Sara / Ahmed, Afeefa / Novik, Laura / Widge, Alicia / Gordon, Ingelise / Guech, Mercy / Teng, I-Ting / Phung, Emily / Ruckwardt, Tracy J / Pegu, Amarendra / Misasi, John / Doria-Rose, Nicole A / Gaudinski, Martin / Koup, Richard A / Kwong, Peter D / McDermott, Adrian B / Amit, Sharon / Schacker, Timothy W / Levy, Itzchak / Mascola, John R / Sullivan, Nancy J / Schramm, Chaim A / Douek, Daniel C

bioRxiv : the preprint server for biology

2022

Abstract: An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope ...

Abstract	An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. The basis for such cross-protection at the molecular level is incompletely understood. Here we characterized the repertoire and epitope specificity of antibodies elicited by Beta, Gamma and ancestral variant infection and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a high-throughput approach to obtain immunoglobulin sequences and produce monoclonal antibodies for functional assessment from single B cells. Infection with any variant elicited similar cross-binding antibody responses exhibiting a remarkably conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may represent a general immunological principle that accounts for the continued efficacy of vaccines based on a single ancestral variant.
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.03.28.486152
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Article ; Online: Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm.

Zunder, Eli R / Finck, Rachel / Behbehani, Gregory K / Amir, El-Ad D / Krishnaswamy, Smita / Gonzalez, Veronica D / Lorang, Cynthia G / Bjornson, Zach / Spitzer, Matthew H / Bodenmiller, Bernd / Fantl, Wendy J / Pe'er, Dana / Nolan, Garry P

Nature protocols

2015 Volume 10, Issue 2, Page(s) 316–333

Abstract: Mass-tag cell barcoding (MCB) labels individual cell samples with unique combinatorial barcodes, after which they are pooled for processing and measurement as a single multiplexed sample. The MCB method eliminates variability between samples in antibody ... ...

Abstract	Mass-tag cell barcoding (MCB) labels individual cell samples with unique combinatorial barcodes, after which they are pooled for processing and measurement as a single multiplexed sample. The MCB method eliminates variability between samples in antibody staining and instrument sensitivity, reduces antibody consumption and shortens instrument measurement time. Here we present an optimized MCB protocol. The use of palladium-based labeling reagents expands the number of measurement channels available for mass cytometry and reduces interference with lanthanide-based antibody measurement. An error-detecting combinatorial barcoding scheme allows cell doublets to be identified and removed from the analysis. A debarcoding algorithm that is single cell-based rather than population-based improves the accuracy and efficiency of sample deconvolution. This debarcoding algorithm has been packaged into software that allows rapid and unbiased sample deconvolution. The MCB procedure takes 3-4 h, not including sample acquisition time of ∼1 h per million cells.
MeSH term(s)	Algorithms ; Flow Cytometry/methods ; Palladium ; Single-Cell Analysis/methods ; Software ; Staining and Labeling/methods
Chemical Substances	Palladium (5TWQ1V240M)
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2244966-8
ISSN	1750-2799 ; 1754-2189
ISSN (online)	1750-2799
ISSN	1754-2189
DOI	10.1038/nprot.2015.020
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Article: Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung

Gagne, Matthew / Corbett, Kizzmekia S. / Flynn, Barbara J. / Foulds, Kathryn E. / Wagner, Danielle A. / Andrew, Shayne F. / Todd, John-Paul M. / Honeycutt, Christopher Cole / McCormick, Lauren / Nurmukhambetova, Saule T. / Davis-Gardner, Meredith E. / Pessaint, Laurent / Bock, Kevin W. / Nagata, Bianca M. / Minai, Mahnaz / Werner, Anne P. / Moliva, Juan I. / Tucker, Courtney / Lorang, Cynthia G. /

Zhao, Bingchun / McCarthy, Elizabeth / Cook, Anthony / Dodson, Alan / Teng, I-Ting / Mudvari, Prakriti / Roberts-Torres, Jesmine / Laboune, Farida / Wang, Lingshu / Goode, Adrienne / Kar, Swagata / Boyoglu-Barnum, Seyhan / Yang, Eun Sung / Shi, Wei / Ploquin, Aurélie / Doria-Rose, Nicole / Carfi, Andrea / Mascola, John R. / Boritz, Eli A. / Edwards, Darin K. / Andersen, Hanne / Lewis, Mark G. / Suthar, Mehul S. / Graham, Barney S. / Roederer, Mario / Moore, Ian N. / Nason, Martha C. / Sullivan, Nancy J. / Douek, Daniel C. / Seder, Robert A.

Cell. 2022 Jan. 06, v. 185, no. 1

2022

Abstract: mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and ... ...

Abstract	mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID₅₀ at weeks 6 (peak) and 48 (challenge), respectively. Antibody-binding titers also decreased in bronchoalveolar lavage (BAL). Four days after Delta challenge, the virus was unculturable in BAL, and subgenomic RNA declined by ∼3-log₁₀ compared with control animals. In nasal swabs, sgRNA was reduced by 1-log₁₀, and the virus remained culturable. Anamnestic antibodies (590-fold increased titer) but not T cell responses were detected in BAL by day 4 post-challenge. mRNA-1273-mediated protection in the lungs is durable but delayed and potentially dependent on anamnestic antibody responses. Rapid and sustained protection in upper and lower airways may eventually require a boost.
Keywords	RNA ; Severe acute respiratory syndrome coronavirus 2 ; T-lymphocytes ; antibodies ; antibody formation ; blood serum ; durability ; lungs ; nose ; vaccination ; vaccines ; viruses
Language	English
Dates of publication	2022-0106
Size	p. 113-130.e15.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.12.002
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.

Miao, Edward A / Mao, Dat P / Yudkovsky, Natalya / Bonneau, Richard / Lorang, Cynthia G / Warren, Sarah E / Leaf, Irina A / Aderem, Alan

Proceedings of the National Academy of Sciences of the United States of America

2010 Volume 107, Issue 7, Page(s) 3076–3080

Abstract: The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the ... ...

Abstract	The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the cytokines IL-1beta and IL-18, whereas certain NLRs trigger their subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type III secretion systems (T3SS) to deliver virulence factors to the cytosol of host cells, where they modulate cell physiology to favor the pathogen. We show here that NLRC4/Ipaf detects the basal body rod component of the T3SS apparatus (rod protein) from S. typhimurium (PrgJ), Burkholderia pseudomallei (BsaK), Escherichia coli (EprJ and EscI), Shigella flexneri (MxiI), and Pseudomonas aeruginosa (PscI). These rod proteins share a sequence motif that is essential for detection by NLRC4; a similar motif is found in flagellin that is also detected by NLRC4. S. typhimurium has two T3SS: Salmonella pathogenicity island-1 (SPI1), which encodes the rod protein PrgJ, and SPI2, which encodes the rod protein SsaI. Although PrgJ is detected by NLRC4, SsaI is not, and this evasion is required for virulence in mice. The detection of a conserved component of the T3SS apparatus enables innate immune responses to virulent bacteria through a single pathway, a strategy that is divergent from that used by plants in which multiple NB-LRR proteins are used to detect T3SS effectors or their effects on cells. Furthermore, the specific detection of the virulence machinery permits the discrimination between pathogenic and nonpathogenic bacteria.
MeSH term(s)	Animals ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/immunology ; Bacterial Infections/immunology ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Bacterial Proteins/metabolism ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/immunology ; Caspase 1/immunology ; Caspase 1/metabolism ; Immunity, Innate/immunology ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Conformation ; Transfection
Chemical Substances	Apoptosis Regulatory Proteins ; Bacterial Proteins ; Calcium-Binding Proteins ; Ipaf protein, mouse ; Membrane Proteins ; SPI-2 protein, Salmonella ; Spi1 protein, Salmonella ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2010-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.0913087107
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Article: Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway.

Gagne, Matthew / Corbett, Kizzmekia S / Flynn, Barbara J / Foulds, Kathryn E / Wagner, Danielle A / Andrew, Shayne F / Todd, John-Paul M / Honeycutt, Christopher Cole / McCormick, Lauren / Nurmukhambetova, Saule T / Davis-Gardner, Meredith E / Pessaint, Laurent / Bock, Kevin W / Nagata, Bianca M / Minai, Mahnaz / Werner, Anne P / Moliva, Juan I / Tucker, Courtney / Lorang, Cynthia G /

Zhao, Bingchun / McCarthy, Elizabeth / Cook, Anthony / Dodson, Alan / Mudvari, Prakriti / Roberts-Torres, Jesmine / Laboune, Farida / Wang, Lingshu / Goode, Adrienne / Kar, Swagata / Boyoglu-Barnum, Seyhan / Yang, Eun Sung / Shi, Wei / Ploquin, Aurélie / Doria-Rose, Nicole / Carfi, Andrea / Mascola, John R / Boritz, Eli A / Edwards, Darin K / Andersen, Hanne / Lewis, Mark G / Suthar, Mehul S / Graham, Barney S / Roederer, Mario / Moore, Ian N / Nason, Martha C / Sullivan, Nancy J / Douek, Daniel C / Seder, Robert A

bioRxiv : the preprint server for biology

2021

Abstract: mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year ... ...

Abstract	mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID
Language	English
Publishing date	2021-10-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.10.23.465542
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Article ; Online: Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones.

Peyton, Lowrey / Narpala, Sandeep R / O'Connell, Sarah / Serebryannyy, Leonid / Wang, Jennifer / Schrager, Alexander / Talana, Chloe Adrienna / Shimberg, Geoffrey / Leung, Kwanyee / Shi, Wei / Khashab, Rawan / Biber, Asaf / Zilberman, Tal / Rhein, Joshua / Vetter, Sara / Ahmed, Afeefa / Novik, Laura / Widge, Alicia / Gordon, Ingelise / Guech, Mercy / Teng, I-Ting / Phung, Emily / Ruckwardt, Tracy J / Pegu, Amarendra / Misasi, John / Doria-Rose, Nicole A / Gaudinski, Martin / Koup, Richard A / Kwong, Peter D / McDermott, Adrian B / Amit, Sharon / Schacker, Timothy W / Levy, Itzchak / Mascola, John R / Sullivan, Nancy J / Schramm, Chaim A / Douek, Daniel C

Nature communications

2022 Volume 13, Issue 1, Page(s) 7733

Abstract: An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here, we characterized the repertoire ... ...

Abstract	An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here, we characterized the repertoire and epitope specificity of antibodies elicited by infection with the Beta, Gamma and WA1 ancestral variants and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a method to obtain immunoglobulin sequences with concurrent rapid production and functional assessment of monoclonal antibodies from hundreds of single B cells sorted by flow cytometry. Infection with any variant elicited similar cross-binding antibody responses exhibiting a conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may account for the continued efficacy of vaccines based on a single ancestral variant.
MeSH term(s)	Humans ; Immunoglobulin Variable Region ; Epitopes/genetics ; SARS-CoV-2/genetics ; COVID-19 ; Clone Cells ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Immunoglobulin Variable Region ; Epitopes ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-12-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-35456-2
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