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Article: Mpox vaccine and infection-driven human immune signatures.

Cohn, Hallie / Bloom, Nathaniel / Cai, Gianna / Clark, Jordan / Tarke, Alison / Bermúdez-González, Maria C / Altman, Deena / Lugo, Luz Amarilis / Lobo, Francisco Pereira / Marquez, Susanna / Chen, Jin-Qiu / Ren, Wenlin / Qin, Lili / Crotty, Shane / Krammer, Florian / Grifoni, Alba / Sette, Alessandro / Simon, Viviana / Coelho, Camila H

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS ... ...

Abstract	Background: Mpox (formerly known as monkeypox) outbreaks outside endemic areas peaked in July 2022, infecting > 85,000 people and raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side effects than previous smallpox vaccines and demonstrated efficacy against mpox infection in humans. Comparing JYNNEOS vaccine- and mpox-induced immunity is imperative to evaluate JYNNEOS' immunogenicity and inform vaccine administration and design. Methods: We examined the polyclonal serum (ELISA) and single B cell (heavy chain gene and transcriptome data) antibody repertoires and T cells (AIM and ICS assays) induced by the JYNNEOS vaccine as well as mpox infection. Findings: Gene-level plasmablast and antibody responses were negligible and JYNNEOS vaccinee sera displayed minimal binding to recombinant mpox proteins and native proteins from the 2022 outbreak strain. In contrast, recent mpox infection (within 20-102 days) induced robust serum antibody responses to A29L, A35R, A33R, B18R, and A30L, and to native mpox proteins, compared to vaccinees. JYNNEOS vaccine recipients presented comparable CD4 and CD8 T cell responses against orthopox peptides to those observed after mpox infection. Interpretation: JYNNEOS immunization does not elicit a robust B cell response, and its immunogenicity may be mediated by T cells. Funding: Research reported in this publication was supported, in part, by the National Cancer Institute of the National Institutes of Health under Award Number U54CA267776, U19AI168631(VS), as well as institutional funds from the Icahn School of Medicine.
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.07.23286701
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Article ; Online: Memory B cell development after asymptomatic or mild symptomatic SARS-CoV-2 infection.

Kato, Yu / Bloom, Nathaniel I / Sun, Peifang / Balinsky, Corey A / Qiu, Qi / Cheng, Ying / Jani, Vihasi / Schilling, Megan A / Goforth, Carl W / Weir, Dawn L / Ramos, Irene / Sealfon, Stuart C / Letizia, Andrew G / Crotty, Shane

The Journal of infectious diseases

2022

Abstract: Background: The development of memory B cells after asymptomatic SARS-CoV-2 infection is not well understood.: Methods: We compared Spike antibody titers, pseudovirus neutralizing antibody titers, and memory B cell responses among SARS-CoV-2 PCR ... ...

Abstract	Background: The development of memory B cells after asymptomatic SARS-CoV-2 infection is not well understood. Methods: We compared Spike antibody titers, pseudovirus neutralizing antibody titers, and memory B cell responses among SARS-CoV-2 PCR positive Marine recruits who either reported asymptomatic or symptomatic infection. Results: 36 asymptomatic participants exhibited similar Spike IgG titers, Spike IgA titers, and pseudovirus neutralization titers compared to 30 symptomatic participants. Pseudovirus neutralization and Spike IgG titers showed significant positive correlations with frequency of memory B cells. Conclusions: Among young adults, asymptomatic SARS-CoV-2 infection induced antibody and memory B cell responses comparable to mild symptomatic infection.
Language	English
Publishing date	2022-07-27
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/jiac319
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Article: Humoral and cellular immune memory to four COVID-19 vaccines.

Zhang, Zeli / Mateus, Jose / Coelho, Camila H / Dan, Jennifer M / Moderbacher, Carolyn Rydyznski / Gálvez, Rosa Isela / Cortes, Fernanda H / Grifoni, Alba / Tarke, Alison / Chang, James / Escarrega, E Alexandar / Kim, Christina / Goodwin, Benjamin / Bloom, Nathaniel I / Frazier, April / Weiskopf, Daniela / Sette, Alessandro / Crotty, Shane

bioRxiv : the preprint server for biology

2022

Abstract: Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be ... ...

Abstract	Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4
Language	English
Publishing date	2022-03-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.03.18.484953
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Article ; Online: Preserved SARS-CoV-2 Vaccine Cell-Mediated Immunogenicity in Patients With Inflammatory Bowel Disease on Immune-Modulating Therapies.

Boland, Brigid S / Goodwin, Benjamin / Zhang, Zeli / Bloom, Nathaniel / Kato, Yu / Neill, Jennifer / Le, Helen / Tysl, Tiffani / Collins, Angelina E / Dulai, Parambir S / Singh, Siddharth / Nguyen, Nghia H / Grifoni, Alba / Sette, Alessandro / Weiskopf, Daniela / Chang, John T / Dan, Jennifer M

Clinical and translational gastroenterology

2022 Volume 13, Issue 4, Page(s) e00484

Abstract: Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after ... ...

Abstract	Immune-modulating medications for inflammatory bowel diseases (IBDs) have been associated with suboptimal vaccine responses. There are conflicting data with SARS-CoV-2 vaccination. We therefore assessed SARS-CoV-2 vaccine immunogenicity at 2 weeks after second mRNA vaccination in 29 patients with IBD compared with 12 normal healthy donors. We observed reduced humoral immunity in patients with IBD on infliximab. However, we observed no difference in humoral and cell-mediated immunity in patients with IBD on infliximab with a thiopurine or vedolizumab compared with normal healthy donors. This is the first study to demonstrate comparable cell-mediated immunity with SARS-CoV-2 vaccination in patients with IBD treated with different immune-modulating medications.
MeSH term(s)	COVID-19/prevention & control ; COVID-19 Vaccines ; Chronic Disease ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Infliximab/pharmacology ; Infliximab/therapeutic use ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2581516-7
ISSN	2155-384X ; 2155-384X
ISSN (online)	2155-384X
ISSN	2155-384X
DOI	10.14309/ctg.0000000000000484
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Article ; Online: Humoral and cellular immune memory to four COVID-19 vaccines.

Cell

2022 Volume 185, Issue 14, Page(s) 2434–2451.e17

Abstract	Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4
MeSH term(s)	Ad26COVS1 ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Immunity, Humoral ; Immunologic Memory ; SARS-CoV-2
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; Antibodies, Viral ; COVID-19 Vaccines ; NVX-CoV2373 adjuvated lipid nanoparticle (2SCD8Q63PF) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.05.022
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Article ; Online: SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron.

Tarke, Alison / Coelho, Camila H / Zhang, Zeli / Dan, Jennifer M / Yu, Esther Dawen / Methot, Nils / Bloom, Nathaniel I / Goodwin, Benjamin / Phillips, Elizabeth / Mallal, Simon / Sidney, John / Filaci, Gilberto / Weiskopf, Daniela / da Silva Antunes, Ricardo / Crotty, Shane / Grifoni, Alba / Sette, Alessandro

Cell

2022 Volume 185, Issue 5, Page(s) 847–859.e11

Abstract: We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By ... ...

Abstract	We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4
MeSH term(s)	Ad26COVS1/administration & dosage ; Ad26COVS1/immunology ; BNT162 Vaccine/administration & dosage ; BNT162 Vaccine/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; COVID-19/pathology ; COVID-19/prevention & control ; COVID-19/virology ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Epitopes/immunology ; Epitopes, T-Lymphocyte/immunology ; Humans ; Memory B Cells/immunology ; Memory B Cells/metabolism ; Memory T Cells/immunology ; Memory T Cells/metabolism ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology ; Vaccination
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; COVID-19 Vaccines ; Epitopes ; Epitopes, T-Lymphocyte ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; NVX-CoV2373 adjuvated lipid nanoparticle (2SCD8Q63PF) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.01.015
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Article ; Online: Mpox vaccine and infection-driven human immune signatures: an immunological analysis of an observational study.

The Lancet. Infectious diseases

2023 Volume 23, Issue 11, Page(s) 1302–1312

Abstract: Background: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox ... ...

Abstract	Background: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. Methods: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. Findings: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6-33 days after the first dose and 5-40 days after the second dose. Mpox-convalescent samples were collected 20-102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20-102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4 Interpretation: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.
MeSH term(s)	United States ; Animals ; Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Mpox (monkeypox)/prevention & control ; Smallpox Vaccine ; Leukocytes, Mononuclear ; Vaccines ; Vaccination ; Monkeypox virus
Chemical Substances	Smallpox Vaccine ; Vaccines
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00352-3
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Article: SARS-CoV-2 monoclonal antibody treatment followed by vaccination shifts human memory B cell epitope recognition suggesting antibody feedback.

Coelho, Camila H / Bloom, Nathaniel / Ramirez, Sydney I / Parikh, Urvi M / Heaps, Amy / Sieg, Scott F / Greninger, Alex / Ritz, Justin / Moser, Carlee / Eron, Joseph J / Currier, Judith S / Klekotka, Paul / Wohl, David A / Daar, Eric S / Li, Jonathan / Hughes, Michael D / Chew, Kara W / Smith, Davey M / Crotty, Shane

bioRxiv : the preprint server for biology

2023

Abstract: Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the ... ...

Abstract	Therapeutic anti-SARS-CoV-2 monoclonal antibodies (mAbs) have been extensively studied in humans, but the impact on immune memory of mAb treatment during an ongoing immune response has remained unclear. Here, we evaluated the effect of infusion of the anti-SARS-CoV-2 spike receptor binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of memory B cells targeting Spike towards non-RBD epitopes. Furthermore, the relative affinity of RBD memory B cells was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA COVID-19 vaccination, memory B cell differences persisted and mapped to a specific defect in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating human memory B cell responses, both to infection and vaccination. These data indicate that mAb administration can promote alterations in the epitopes recognized by the B cell repertoire, and the single administration of mAb can continue to determine the fate of B cells in response to additional antigen exposures months later.
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.21.567575
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Article: Humoral and cellular immune memory to four COVID-19 vaccines

Zhang, Zeli / Mateus, Jose / Coelho, Camila H. / Dan, Jennifer M. / Moderbacher, Carolyn Rydyznski / Gálvez, Rosa Isela / Cortes, Fernanda H. / Grifoni, Alba / Tarke, Alison / Chang, James / Escarrega, E. Alexandar / Kim, Christina / Goodwin, Benjamin / Bloom, Nathaniel I. / Frazier, April / Weiskopf, Daniela / Sette, Alessandro / Crotty, Shane

Cell. 2022 July 07, v. 185, no. 14

2022

Abstract	Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4⁺ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8⁺ T cell frequencies, though only detectable in 60–67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3⁺ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.
Keywords	B-lymphocytes ; COVID-19 infection ; antibodies ; immunologic memory ; memory ; vaccination ; vaccines
Language	English
Dates of publication	2022-0707
Size	p. 2434-2451.e17.
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.2022.05.022
Database	NAL-Catalogue (AGRICOLA)

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Article: SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron

Tarke, Alison / Coelho, Camila H. / Zhang, Zeli / Dan, Jennifer M. / Yu, Esther Dawen / Methot, Nils / Bloom, Nathaniel I. / Goodwin, Benjamin / Phillips, Elizabeth / Mallal, Simon / Sidney, John / Filaci, Gilberto / Weiskopf, Daniela / da Silva Antunes, Ricardo / Crotty, Shane / Grifoni, Alba / Sette, Alessandro

Cell. 2022 Mar. 03, v. 185, no. 5

2022

Abstract	We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4⁺) and 87% (CD8⁺) of memory T cell responses were preserved against variants on average by AIM assay, and 84% (CD4⁺) and 85% (CD8⁺) preserved against Omicron. Omicron RBD memory B cell recognition was substantially reduced to 42% compared with other variants. T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4⁺ and CD8⁺ T cells, with average preservation > 80% for Omicron. Functional preservation of the majority of T cell responses may play an important role as a second-level defense against diverse variants.
Keywords	B-lymphocytes ; Severe acute respiratory syndrome coronavirus 2 ; epitopes ; memory ; vaccination ; vaccines
Language	English
Dates of publication	2022-0303
Size	p. 847-859.e11.
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.2022.01.015
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