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Article ; Online: Fantastic IgA plasma cells and where to find them.

Isho, Baweleta / Florescu, Alexandra / Wang, Angela A / Gommerman, Jennifer L

2021 Volume 303, Issue 1, Page(s) 119–137

Abstract: IgA is produced in large quantities at mucosal surfaces by ... ...

Abstract	IgA is produced in large quantities at mucosal surfaces by IgA
MeSH term(s)	Immunoglobulin A ; Intestinal Mucosa ; Lymph Nodes ; Peyer's Patches ; Plasma Cells
Chemical Substances	Immunoglobulin A
Language	English
Publishing date	2021-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12980
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Article ; Online: The Impact of IgA and the Microbiota on CNS Disease.

Pu, Annie / Lee, Dennis S W / Isho, Baweleta / Naouar, Ikbel / Gommerman, Jennifer L

Frontiers in immunology

2021 Volume 12, Page(s) 742173

Abstract: Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial ... ...

Abstract	Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial derived metabolites that modulate neuroinflammation and neurodegeneration have provided mechanistic insight into how the gut may modulate the CNS. Furthermore, the participation of the gut in regulation of peripheral and CNS immune activity introduces a potential therapeutic target. This review addresses emerging literature on how the microbiome can affect glia and circulating lymphocytes in preclinical models of human CNS disease. Critically, this review also discusses how the host may in turn influence the microbiome, and how this may impact CNS homeostasis and disease, potentially through the production of IgA.
MeSH term(s)	Animals ; Central Nervous System Diseases/immunology ; Gastrointestinal Microbiome/immunology ; Humans ; Immunoglobulin A/immunology ; Neuroimmunomodulation/immunology ; Neuroinflammatory Diseases/immunology
Chemical Substances	Immunoglobulin A
Language	English
Publishing date	2021-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.742173
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Article ; Online: Persistence of T Cell and Antibody Responses to SARS-CoV-2 Up to 9 Months after Symptom Onset.

Law, Jaclyn C / Girard, Melanie / Chao, Gary Y C / Ward, Lesley A / Isho, Baweleta / Rathod, Bhavisha / Colwill, Karen / Li, Zhijie / Rini, James M / Yue, Feng Yun / Mubareka, Samira / McGeer, Allison J / Ostrowski, Mario A / Gommerman, Jennifer L / Gingras, Anne-Claude / Watts, Tania H

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 208, Issue 2, Page(s) 429–443

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. In this study, we followed T cell and Ab responses in 24 mainly nonhospitalized human subjects who had recovered from PCR-confirmed SARS-CoV-2 infection at two time points (median of 45 and 145 d after symptom onset). Ab responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-spike (anti-S) and anti-receptor binding domain IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. T cell responses to SARS-CoV-2 peptides were determined using intracellular cytokine staining, activation markers, proliferation, and cytokine secretion. All study subjects had a T cell response to at least one SARS-CoV-2 Ag based on at least one T cell assay. CD4
MeSH term(s)	Adult ; Aged ; Antibody Formation ; COVID-19/immunology ; Female ; Humans ; Immunity, Cellular ; Immunoglobulin G/immunology ; Male ; Middle Aged ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Th1 Cells/immunology ; Time Factors
Chemical Substances	Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Observational Study
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.2100727
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Article ; Online: Immunity to SARS-CoV-2 persists 9 months post-symptoms with an altered T cell phenotype compared to influenza A virus-specific memory

Law, Jaclyn C / Girard, Melanie / Chao, Gary Y.C. / Ward, Lesley A / Isho, Baweleta / Rathod, Bhavisha / Colwill, Karen / Li, Zhijie / Rini, James M / Yue, Feng Yun / Mubareka, Samira / McGeer, Allison J / Ostrowski, Mario A / Gommerman, Jennifer L / Gingras, Anne-Claude / Watts, Tania H

medRxiv

Abstract: SARS-CoV-2 induces T cell, B cell and antibody responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. Here we followed T cell and antibody ... ...

Abstract	SARS-CoV-2 induces T cell, B cell and antibody responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. Here we followed T cell and antibody responses in 24 mainly non-hospitalized SARS-CoV-2 recovered subjects at two time points (median of 45- and 145-days post-symptom onset). Antibody responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-S and anti-RBD IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. Based on intracellular cytokine production or proliferation, CD4+ T cell responses to SARS-CoV-2 were detected in all subjects, decaying with a half-life of 5-6 months for S-specific IL-2-producing cells. CD4+ responses were largely of the T helper 1 phenotype, but with a lower ratio of IFN-γ : IL-2 producing cells and a lower frequency of CD8+: CD4+ T cells compared to influenza A virus-(IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ: IL-2 and IFN-γ: IL-6 and an altered cytotoxic profile for S- and N-specific compared to IAV-specific responses. These data suggest that the memory T-cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxic profile compared to long term memory to IAV within the same subjects.
Keywords	covid19
Language	English
Publishing date	2021-06-10
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.06.08.21258518
Database	COVID19

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Article ; Online: Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection.

Sheikh-Mohamed, Salma / Isho, Baweleta / Chao, Gary Y C / Zuo, Michelle / Cohen, Carmit / Lustig, Yaniv / Nahass, George R / Salomon-Shulman, Rachel E / Blacker, Grace / Fazel-Zarandi, Mahya / Rathod, Bhavisha / Colwill, Karen / Jamal, Alainna / Li, Zhijie / de Launay, Keelia Quinn / Takaoka, Alyson / Garnham-Takaoka, Julia / Patel, Anjali / Fahim, Christine /

Mucosal immunology

2022 Volume 15, Issue 5, Page(s) 799–808

Abstract: Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants ... ...

Abstract	Although SARS-CoV-2 infects the upper respiratory tract, we know little about the amount, type, and kinetics of antibodies (Ab) generated in the oral cavity in response to COVID-19 vaccination. We collected serum and saliva samples from participants receiving two doses of mRNA COVID-19 vaccines and measured the level of anti-SARS-CoV-2 Ab. We detected anti-Spike and anti-Receptor Binding Domain (RBD) IgG and IgA, as well as anti-Spike/RBD associated secretory component in the saliva of most participants after dose 1. Administration of a second dose of mRNA boosted the IgG but not the IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants exhibited diminished anti-Spike/RBD IgG levels, although secretory component-associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 variants had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2-4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. Our study finds that a local secretory component-associated IgA response is induced by COVID-19 mRNA vaccination that persists in some, but not all participants. The serum and saliva IgA response modestly correlate at 2-4 weeks post-dose 2. Of note, levels of anti-Spike serum IgA (but not IgG) at this timepoint are lower in participants who subsequently become infected with SARS-CoV-2. As new surges of SARS-CoV-2 variants arise, developing COVID-19 booster shots that provoke high levels of IgA has the potential to reduce person-to-person transmission.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Prospective Studies ; RNA, Messenger/genetics ; SARS-CoV-2 ; Secretory Component ; Vaccination ; Viral Vaccines
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Secretory Component ; Viral Vaccines
Language	English
Publishing date	2022-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-022-00511-0
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Article ; Online: A mucosal antibody response is induced by intra-muscular SARS-CoV-2 mRNA vaccination

Mohamed, Salma Sheikh / Chao, Gary Y.C. / Isho, Baweleta / Zuo, Michelle / Nahass, George R. / Salomon-Shulman, Rachel E. / Blacker, Grace / Fazel-Zarandi, Mahya / Rathod, Bhavisha / Colwell, Karen / Jamal, Alainna / Li, Zhijie / Quinn de Launay, Keelia / Takaoka, Alyson / Fahim, Christine / Paterson, Aimee / Li, Angel / Garnham-Takaoka, Julia / Haq, Nazrana /

Barati, Shiva / Gilbert, Lois / Green, Karen / Mozafarihashjin, Mohammad / Samaan, Philip / Siqueira, Walter L / Mubareka, Samira / Ostrowski, Mario A / Rini, James / Rojas, Olga / McGeer, Allison / Weissman, Irving L / Caspi-Tal, Michal / Strauss, Sharon / Gingras, Anne-Claude / Gommerman, Jen

medRxiv

Abstract: Vaccines against SARS-CoV-2 administered via the parenteral route (intra-muscular = i.m.) are effective at preventing COVID-19 in part by inducing neutralizing antibodies in the blood. The first line of defense against SARS-CoV-2 is in the upper ... ...

Abstract	Vaccines against SARS-CoV-2 administered via the parenteral route (intra-muscular = i.m.) are effective at preventing COVID-19 in part by inducing neutralizing antibodies in the blood. The first line of defense against SARS-CoV-2 is in the upper respiratory tract, yet we know very little about whether COVID-19 vaccines induce immunity in this compartment, if at all. We analysed salivary antibodies against the SARS-CoV-2 Spike protein and its receptor binding domain (RBD) following 2 i.m. injections of either BNT162b2 or mRNA-1273 vaccines. Salivary anti-Spike/RBD IgG was detected after 1 dose and increased further after dose 2, reflecting the systemic immune response. Interestingly, salivary anti-Spike/RBD IgA associated with the secretory component (sIgA) was detected in nearly all vaccinated participants after one dose of mRNA vaccine, with anti-Spike sIgA diminishing after dose 2. Vaccination with ChAdOx1-S (Ad) followed by mRNA induced similar levels of salivary anti-Spike/RBD IgG and IgA, and both mRNA/mRNA and Ad/mRNA regimes provoked modest neutralizing capacity in this biofluid. Our results demonstrate that SARS-CoV-2 mRNA/mRNA and Ad/mRNA vaccination induces antibodies in the saliva, and in response to one dose of mRNA, a compartmentalized and transient antigen-specific sIgA response is generated that does not correlate with systemic immunity.
Keywords	covid19
Language	English
Publishing date	2021-08-04
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.08.01.21261297
Database	COVID19

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Article ; Online: Intramuscular SARS-CoV-2 vaccines elicit varying degrees of plasma and salivary antibody responses as compared to natural infection

Nahass, George Ronald / Salomon-Shulman, Rachel E / Blacker, Grace / Haider, Kazim / Brotherton, Rich / Teague, Kristine / Yiu, Ying Ying / Brewer, Rachel E. / Galloway, Sarah Danielle / Hansen, Paige / Marquez-Arreguin, Gabriel / Sheikh-Mohamed, Salma / Chao, Gary Y.C. / Isho, Baweleta / Do, Evan / Chang, Iris / Snow, Theo / Lee, Alexandra S. / STANFORD COVID-19 BIOBANK /

Manohar, Monali / Yang, Samuel / Blomkalns, Andra L. / Rogers, Angela J. / McGeer, Allison / Gingras, Anne-Claude / Straus, Sharon / Grant, Phillip / Nadeau, Kari C. / Blish, Catherine A. / Gommerman, Jennifer L. / Sanders, Erin C. / Weissman, Irving L. / Tal, Michal Caspi

medRxiv

Abstract: Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or ... ...

Abstract	Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2.
Keywords	covid19
Language	English
Publishing date	2021-08-30
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.08.22.21262168
Database	COVID19

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Article ; Online: Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients.

Isho, Baweleta / Abe, Kento T / Zuo, Michelle / Jamal, Alainna J / Rathod, Bhavisha / Wang, Jenny H / Li, Zhijie / Chao, Gary / Rojas, Olga L / Bang, Yeo Myong / Pu, Annie / Christie-Holmes, Natasha / Gervais, Christian / Ceccarelli, Derek / Samavarchi-Tehrani, Payman / Guvenc, Furkan / Budylowski, Patrick / Li, Angel / Paterson, Aimee /

Yue, Feng Yun / Marin, Lina M / Caldwell, Lauren / Wrana, Jeffrey L / Colwill, Karen / Sicheri, Frank / Mubareka, Samira / Gray-Owen, Scott D / Drews, Steven J / Siqueira, Walter L / Barrios-Rodiles, Miriam / Ostrowski, Mario / Rini, James M / Durocher, Yves / McGeer, Allison J / Gommerman, Jennifer L / Gingras, Anne-Claude

Science immunology

2020 Volume 5, Issue 52

Abstract: While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays ( ... ...

Abstract	While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.
MeSH term(s)	Adult ; Antibodies, Viral/blood ; Antigens, Viral/immunology ; Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Cross-Sectional Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin A/blood ; Immunoglobulin A/immunology ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Immunoglobulin M/blood ; Immunoglobulin M/immunology ; Longitudinal Studies ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Saliva/immunology ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-10-08
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abe5511
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evidence for sustained mucosal and systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients

Feng Yun, Yue / Marin, Lina G / Caldwell, Lauren / Wrana, Jeffrey L / Colwill, Karen / Sicheri, Frank / Mubareka, Samira / Gray-Owen, Scott D / Drews, Steven J / Siqueira, Walter L / Barrios-Rodiles, Miriam / Ostrowski, Mario / Rini, James M / Durocher, Yves / McGeer, Allison J / Gommerman, Jennifer L / Gingras, Anne-Claude

medRxiv

Abstract: While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the ...

Abstract	While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection. We developed enzyme linked immunosorbent assays to detect IgA and IgG antibodies to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA antibodies rapidly decayed, IgG antibodies remained relatively stable up to 115 days PSO in both biofluids. Importantly, IgG responses in saliva and serum were correlated, suggesting that antibodies in the saliva may serve as a surrogate measure of systemic immunity.
Keywords	covid19
Language	English
Publishing date	2020-08-04
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.08.01.20166553
Database	COVID19

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Article: Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients

Sci. immunol

Abstract	While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #842548
Database	COVID19

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