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Article ; Online: The benefit of boosters: diversity and inclusion in the COVID-19 memory response.

Hartley, Gemma E / van Zelm, Menno C / Robinson, Marcus J

2021 Volume 100, Issue 1, Page(s) 15–17

Abstract: In a new study, a group evaluate immune responses against SARS-CoV-2 in vaccinated individuals and find evidence of durable immune memory for at least 6 months, irrespective of former infection. ...

Abstract	In a new study, a group evaluate immune responses against SARS-CoV-2 in vaccinated individuals and find evidence of durable immune memory for at least 6 months, irrespective of former infection.
MeSH term(s)	COVID-19 ; Cultural Diversity ; Humans ; SARS-CoV-2
Language	English
Publishing date	2021-12-05
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12511
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Article ; Online: New insights into human immune memory from SARS-CoV-2 infection and vaccination.

Hartley, Gemma E / Edwards, Emily S J / O'Hehir, Robyn E / van Zelm, Menno C

Allergy

2022 Volume 77, Issue 12, Page(s) 3553–3566

Abstract: Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS-CoV-2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and ... ...

Abstract	Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS-CoV-2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS-CoV-2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan-based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
MeSH term(s)	Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; Immunologic Memory ; Vaccination ; Pandemics
Language	English
Publishing date	2022-09-20
Publishing country	Denmark
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15502
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Article ; Online: New insights into human immune memory from SARS‐CoV‐2 infection and vaccination

Hartley, Gemma E. / Edwards, Emily S. J. / O’Hehir, Robyn E. / van Zelm, Menno C.

Allergy 2022 Dec., v. 78, no. 4 p. 3553-3566

2022

Abstract: Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and ... ...

Abstract	Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; antibodies ; disease severity ; durability ; humans ; hypersensitivity ; immune response ; immunologic memory ; morbidity ; pandemic ; vaccination
Language	English
Dates of publication	2022-12
Size	p. 3553-3566
Publishing place	John Wiley & Sons, Inc
Document type	Article ; Online
Note	REVIEW ; Resource is Open Access ; Wiley License Information
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15502
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Article ; Online: Humoral immunity and B-cell memory in response to SARS-CoV-2 infection and vaccination.

Fryer, Holly A / Hartley, Gemma E / Edwards, Emily S J / O'Hehir, Robyn E / van Zelm, Menno C

Biochemical Society transactions

2022

Abstract: Natural infection with SARS-CoV-2 induces a robust circulating memory B cell (Bmem) population, which remains stable in number at least 8 months post-infection despite the contraction of antibody levels after 1 month. Multiple vaccines have been ... ...

Abstract	Natural infection with SARS-CoV-2 induces a robust circulating memory B cell (Bmem) population, which remains stable in number at least 8 months post-infection despite the contraction of antibody levels after 1 month. Multiple vaccines have been developed to combat the virus. These include two new formulations, mRNA and adenoviral vector vaccines, which have varying efficacy rates, potentially related to their distinct capacities to induce humoral immune responses. The mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) elicit significantly higher serum IgG and neutralizing antibody levels than the adenoviral vector ChAdOx1 (AstraZeneca) and Ad26.COV2.S (Janssen) vaccines. However, all vaccines induce Spike- and RBD-specific Bmem, which are vital in providing long-lasting protection in the form of rapid recall responses to subsequent infections. Past and current SARS-CoV-2 variants of concern (VoC) have shown the capacity to escape antibody neutralization to varying degrees. A booster dose with an mRNA vaccine following primary vaccination restores antibody levels and improves the capacity of these antibodies and Bmem to bind viral variants, including the current VoC Omicron. Future experimental research will be essential to evaluate the durability of protection against VoC provided by each vaccine and to identify immune markers of protection to enable prognostication of people who are at risk of severe complications from COVID-19.
Language	English
Publishing date	2022-11-24
Publishing country	England
Document type	Journal Article
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20220415
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Article ; Online: COVID-19 Adenoviral Vector Vaccination Elicits a Robust Memory B Cell Response with the Capacity to Recognize Omicron BA.2 and BA.5 Variants.

Fryer, Holly A / Hartley, Gemma E / Edwards, Emily S J / Varese, Nirupama / Boo, Irene / Bornheimer, Scott J / Hogarth, P Mark / Drummer, Heidi E / O'Hehir, Robyn E / van Zelm, Menno C

Journal of clinical immunology

2023 Volume 43, Issue 7, Page(s) 1506–1518

Abstract: Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe ... ...

Abstract	Following the COVID-19 pandemic, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the SARS-CoV-2 Spike receptor-binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response to mRNA BNT162b2 (Pfizer-BioNTech) vaccination. Whole blood was sampled from 31 healthy adults pre-vaccination and 4 weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each time point. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1 and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.
MeSH term(s)	Adult ; Humans ; BNT162 Vaccine ; Memory B Cells ; Pandemics ; COVID-19/prevention & control ; SARS-CoV-2 ; Vaccination ; Adenoviridae ; Antibodies, Neutralizing ; Immunoglobulin G ; Antibodies, Viral
Chemical Substances	BNT162 Vaccine ; Antibodies, Neutralizing ; Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2023-06-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-023-01527-2
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Zs.A 1640: Show issues

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Article ; Online: The second COVID-19 mRNA vaccine dose enhances the capacity of Spike-specific memory B cells to bind Omicron BA.2.

Hartley, Gemma E / Edwards, Emily S J / Varese, Nirupama / Boo, Irene / Aui, Pei M / Bornheimer, Scott J / Hogarth, P Mark / Drummer, Heidi E / O'Hehir, Robyn E / van Zelm, Menno C

Allergy

2022 Volume 78, Issue 3, Page(s) 855–858

MeSH term(s)	Humans ; COVID-19/prevention & control ; COVID-19 Vaccines ; Memory B Cells ; Antibodies, Neutralizing ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing
Language	English
Publishing date	2022-12-30
Publishing country	Denmark
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15624
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Article ; Online: Corrigendum: Fc engineered ACE2-Fc is a potent multifunctional agent targeting SARS-CoV2.

Wines, Bruce D / Kurtovic, Liriye / Trist, Halina M / Esparon, Sandra / Lopez, Ester / Chappin, Klasina / Chan, Li-Jin / Mordant, Francesca L / Lee, Wen Shi / Gherardin, Nicholas A / Patel, Sheila K / Hartley, Gemma E / Pymm, Phillip / Cooney, James P / Beeson, James G / Godfrey, Dale I / Burrell, Louise M / van Zelm, Menno C / Wheatley, Adam K /

Chung, Amy W / Tham, Wai-Hong / Subbarao, Kanta / Kent, Stephen J / Hogarth, P Mark

Frontiers in immunology

2023 Volume 13, Page(s) 1122516

Abstract: This corrects the article .]. ...

Abstract	[This corrects the article .].
Language	English
Publishing date	2023-01-10
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1122516
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Article ; Online: COVID-19 adenoviral vector vaccination elicits a robust memory B cell response with the capacity to recognize Omicron BA.2 and BA.5 variants

Fryer, Holly A. / Hartley, Gemma E. / Edwards, Emily S.J. / Varese, Nirupama / Boo, Irene / Bornheimer, Scott J. / Hogarth, P. Mark / Drummer, Heidi E. / O'Hehir, Robyn E. / van Zelm, Menno C

bioRxiv

Abstract: Following the COVID-19 pandemic caused by SARS-CoV-2, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, ... ...

Abstract	Following the COVID-19 pandemic caused by SARS-CoV-2, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the Spike receptor binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response elicited by the mRNA vaccine BNT162b2 (Pfizer-BioNTech). Whole blood was sampled from 31 healthy adults pre-vaccination, and four weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each timepoint. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1, and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.
Keywords	covid19
Language	English
Publishing date	2023-03-01
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.02.28.530547
Database	COVID19

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Article ; Online: Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after mRNA but not adenovirus priming

Hartley, Gemma E. / Fryer, Holly A. / Gill, Paul A. / Boo, Irene / Bornheimer, Scott J. / Hogarth, P. Mark / Drummer, Heidi E. / O’Hehir, Robyn E. / Edwards, Emily S.J. / van Zelm, Menno C.

bioRxiv

Abstract: Background: Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially ...

Abstract	Background: Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We here examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Methods: Healthy adults who received primary BNT162b2 (mRNA) (n=18) or ChAdOx1 (vector) (n=25) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Results: Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5-20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. Conclusion: A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.
Keywords	covid19
Language	English
Publishing date	2023-09-19
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.09.15.557929
Database	COVID19

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Article ; Online: Third dose COVID-19 mRNA vaccine enhances IgG4 isotype switching and recognition of Omicron subvariants by memory B cells after with mRNA but not adenovirus priming

Hartley, Gemma E. / Fryer, Holly A. / Gill, Paul A. / Boo, Irene / Bornheimer, Scott J. / Hogarth, P. Mark / Drummer, Heidi E. / O'Hehir, Robyn E. / Edwards, Emily S.J. / van Zelm, Menno C.

bioRxiv

Abstract	Background: Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We here examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Methods: Healthy adults who received primary BNT162b2 (mRNA) (n=18) or ChAdOx1 (vector) (n=25) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Results: Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5-20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. Conclusion: A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.
Keywords	covid19
Language	English
Publishing date	2023-09-18
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.09.15.557929
Database	COVID19

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