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Article ; Online: Preserved recognition of Omicron spike following COVID-19 messenger RNA vaccination in pregnancy.

Bartsch, Yannic C / Atyeo, Caroline / Kang, Jaewon / Cai, Yongfei / Chen, Bing / Gray, Kathryn J / Edlow, Andrea G / Alter, Galit

American journal of obstetrics and gynecology

2022 Volume 227, Issue 3, Page(s) 493.e1–493.e7

Abstract: Background: SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated ... ...

Abstract	Background: SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the Centers for Disease Control and Prevention and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns, including the Omicron variant, raised new concerns about vaccine efficacy because of their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following infection with the Omicron variant in vaccinated individuals. Thus, these data suggest that alternate vaccine-induced immunity beyond neutralization may continue to attenuate Omicron variant-induced disease, such as Fc-mediated antibody activity. Objective: This study aimed to test whether vaccine-induced antibodies raised during pregnancy continue to bind to and leverage Fc receptors to protect against variants of concern including the Omicron variant. Study design: The receptor binding domain or whole spike-specific antibody isotype binding titers and Fc gamma receptor binding directed toward variants of concern, including the Omicron variant, were analyzed in pregnant women after receiving the full dose regimen of either the Pfizer/BioNTech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay. Results: Reduced isotype recognition of the Omicron receptor binding domain was observed following administration of either vaccine with relatively preserved, albeit reduced, recognition of the whole Omicron spike by immunoglobulin M and G antibodies. Despite the near complete loss of Fc receptor binding to the Omicron receptor binding domain, Fc receptor binding to the Omicron spike was more variable but largely preserved. Conclusion: Reduced binding titers to the Omicron receptor binding domain aligns with the observed loss of neutralizing activity. Despite the loss of neutralization, preserved, albeit reduced, Omicron spike recognition and Fc receptor binding potentially continue to attenuate disease severity in pregnant women.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Female ; Humans ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Pregnancy ; Pregnancy Complications, Infectious/prevention & control ; RNA, Messenger ; Receptors, Fc ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics ; Vaccination ; Vaccines ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Membrane Glycoproteins ; RNA, Messenger ; Receptors, Fc ; Spike Glycoprotein, Coronavirus ; Vaccines ; Viral Envelope Proteins ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2022.04.009
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Article ; Online: Preserved recognition of Omicron Spike following COVID-19 mRNA vaccination in pregnancy

Bartsch, Yannic C / Atyeo, Caroline / Kang, Jaewon / Gray, Kathryn J / Edlow, Andrea G. / Alter, Galit

medRxiv

Abstract: Summary Background SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated ... ...

Abstract	Summary Background SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the CDC and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns (VOC) including the Omicron VOC raised new concerns about vaccine efficacy, given their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following omicron VOC infection in vaccinated individuals. Thus, these data suggest that alternate vaccine induced immunity, beyond neutralization, may continue to attenuate omicron disease, such as antibody-Fc-mediated activity. However, whether vaccine induced antibodies raised in pregnancy continue to bind and leverage Fc-receptors remains unclear. Methods VOC including Omicron receptor binding domain (RBD) or full Spike specific antibody isotype binding titers and FcγR binding were analyzed in pregnant women after the full dose regimen of either Pfizer/BioNtech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay. Findings Comparable, albeit reduced, isotype recognition was observed to the Omicron Spike and receptor binding domain (RBD) following both vaccines. Yet, despite the near complete loss of Fc-receptor binding to the Omicron RBD, Fc-receptor binding was largely preserved to the Omicron Spike. Interpretation Reduced binding titer to the Omicron RBD aligns with observed loss of neutralizing activity. Despite the loss of neutralization, preserved Omicron Spike recognition and Fc-receptor binding potentially continues to attenuate disease severity in pregnant women. Funding NIH and the Bill and Melinda Gates Foundation
Keywords	covid19
Language	English
Publishing date	2022-01-02
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.01.01.22268615
Database	COVID19

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Article ; Online: Selective SARS-CoV2 BA.2 escape of antibody Fc/Fc-receptor interactions.

Bartsch, Yannic C / Cizmeci, Deniz / Kang, Jaewon / Gao, Hailong / Shi, Wei / Chandrashekar, Abishek / Collier, Ai-Ris Y / Chen, Bing / Barouch, Dan H / Alter, Galit

iScience

2023 Volume 26, Issue 5, Page(s) 106582

Abstract: The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely linked to ... ...

Abstract	The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of new sublineage BA.2, which is more transmissible than BA.1 despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine-induced responses. Here, we comprehensively profiled the BNT162b2 vaccine-induced response to several VOCs, including omicron BA.1 and BA.2. While vaccine-induced immune responses were compromised against both omicron sublineages, vaccine-induced antibody isotype titers, and non-neutralizing Fc effector functions were attenuated to the omicron BA.2 spike compared to BA.1. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2, albeit lower than BA.1 responses, potentially contributing to persistent protection against severity of disease.
Language	English
Publishing date	2023-04-07
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106582
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Article ; Online: Vaccine-induced antibody Fc-effector functions in humans immunized with a combination Ad26.RSV.preF/RSV preF protein vaccine.

Bartsch, Yannic C / Cizmeci, Deniz / Yuan, Dansu / Mehta, Nickita / Tolboom, Jeroen / De Paepe, Els / van Heesbeen, Roy / Sadoff, Jerald / Comeaux, Christy A / Heijnen, Esther / Callendret, Benoit / Alter, Galit / Bastian, Arangassery Rosemary

Journal of virology

2023 Volume 97, Issue 11, Page(s) e0077123

Abstract: Importance: Respiratory syncytial virus (RSV) can cause serious illness in older adults (i.e., those aged ≥60 years). Because options for RSV prophylaxis and treatment are limited, the prevention of RSV-mediated illness in older adults remains an ... ...

Abstract	Importance: Respiratory syncytial virus (RSV) can cause serious illness in older adults (i.e., those aged ≥60 years). Because options for RSV prophylaxis and treatment are limited, the prevention of RSV-mediated illness in older adults remains an important unmet medical need. Data from prior studies suggest that Fc-effector functions are important for protection against RSV infection. In this work, we show that the investigational Ad26.RSV.preF/RSV preF protein vaccine induced Fc-effector functional immune responses in adults aged ≥60 years who were enrolled in a phase 1/2a regimen selection study of Ad26.RSV.preF/RSV preF protein. These results demonstrate the breadth of the immune responses induced by the Ad26.RSV.preF/RSV preF protein vaccine.
MeSH term(s)	Aged ; Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin Fc Fragments ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus Vaccines/immunology ; Respiratory Syncytial Virus, Human ; Viral Fusion Proteins/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin Fc Fragments ; Respiratory Syncytial Virus Vaccines ; Viral Fusion Proteins
Language	English
Publishing date	2023-10-30
Publishing country	United States
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00771-23
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Article ; Online: Long-term humoral signatures following acute pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children.

Burns, Madeleine D / Bartsch, Yannic C / Davis, Jameson P / Boribong, Brittany P / Loiselle, Maggie / Kang, Jaewon / Kane, Abigail S / Edlow, Andrea G / Fasano, Alessio / Alter, Galit / Yonker, Lael M

Pediatric research

2023 Volume 94, Issue 4, Page(s) 1327–1334

Abstract: Background: Although most children experience mild symptoms during acute SARS-CoV-2 infection, some develop the severe post-COVID-19 complication, Multisystem Inflammatory Syndrome in Children (MIS-C). While acute presentations of COVID-19 and MIS-C ... ...

Abstract	Background: Although most children experience mild symptoms during acute SARS-CoV-2 infection, some develop the severe post-COVID-19 complication, Multisystem Inflammatory Syndrome in Children (MIS-C). While acute presentations of COVID-19 and MIS-C have been well immunophenotyped, little is known about the lasting immune profile in children after acute illness. Methods: Children 2 months-20 years of age presenting with either acute COVID-19 (n = 9) or MIS-C (n = 12) were enrolled in a Pediatric COVID-19 Biorepository at a single medical center. We deeply profiled humoral immune responses and circulating cytokines following pediatric COVID-19 and MIS-C. Results: Twenty-one children and young adults provided blood samples at both acute presentation and 6-month follow-up (mean: 6.5 months; standard deviation: 1.77 months). Pro-inflammatory cytokine elevations resolved after both acute COVID-19 and MIS-C. Humoral profiles continue to mature after acute COVID-19, displaying decreasing IgM and increasing IgG over time, as well as stronger effector functions, including antibody-dependent monocyte activation. In contrast, MIS-C immune signatures, especially anti-Spike IgG1, diminished over time. Conclusions: Here, we show the mature immune signature after pediatric COVID-19 and MIS-C, displaying resolving inflammation with recalibration of the humoral responses. These humoral profiles highlight immune activation and vulnerabilities over time in these pediatric post-infectious cohorts. Impact: The pediatric immune profile matures after both COVID-19 and MIS-C, suggesting a diversified anti-SARS-CoV-2 antibody response after resolution of acute illness. While pro-inflammatory cytokine responses resolve in the months following acute infection in both conditions, antibody-activated responses remain relatively heightened in convalescent COVID-19. These data may inform long-term immunoprotection from reinfection in children with past SARS-CoV-2 infections or MIS-C.
MeSH term(s)	Young Adult ; Child ; Humans ; COVID-19/diagnosis ; SARS-CoV-2 ; Acute Disease ; Systemic Inflammatory Response Syndrome/diagnosis ; Cytokines ; Antibodies, Viral
Chemical Substances	Cytokines ; Antibodies, Viral
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-023-02627-w
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Article: Durability and cross-reactivity of SARS-CoV-2 mRNA vaccine in adolescent children.

Burns, Madeleine D / Boribong, Brittany P / Bartsch, Yannic C / Loiselle, Maggie / Davis, Jameson P / Lima, Rosiane / Edlow, Andrea G / Fasano, Alessio / Alter, Galit / Yonker, Lael M

medRxiv : the preprint server for health sciences

2022

Abstract: Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for ... ...

Abstract	Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. We tested the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the SARS-CoV-2 wild type and Omicron antigens. Serum from 77 adolescents showed that anti-Spike antibodies wane significantly over 6 months. After completion of a two-vaccine series, cross-reactivity against Omicron-specific receptor-binding domain (RBD) was seen. Evidence of waning mRNA-induced vaccine immunity underscores vulnerabilities in long-term pediatric protection against SARS-CoV-2 infection, while cross-reactivity highlights the additional benefits of vaccination. Characterization of adolescent immune signatures post-vaccination will inform guidance on vaccine platforms and timelines, and ultimately optimize immunoprotection of children.
Language	English
Publishing date	2022-02-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.01.05.22268617
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Article ; Online: BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children.

Bartsch, Yannic C / Chen, Jessica W / Kang, Jaewon / Burns, Madeleine D / St Denis, Kerri J / Sheehan, Maegan L / Davis, Jameson P / Edlow, Andrea G / Balazs, Alejandro B / Yonker, Lael M / Alter, Galit

NPJ vaccines

2022 Volume 7, Issue 1, Page(s) 158

Abstract: Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of variants of concerns (VOCs) has highlighted the importance of high population-based vaccine rates to effectively ... ...

Abstract	Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of variants of concerns (VOCs) has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine-induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of VOCs that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine-induced antibody titers in children 5-11 years receiving two doses of the age-recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12-15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-VOC responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to VOCs in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2-induced antibody response in children, vaccine-induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to the attenuation of disease.
Language	English
Publishing date	2022-12-03
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-022-00575-w
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Article ; Online: Evolution of functional antibodies following acute Epstein-Barr virus infection.

Karsten, Christina B / Bartsch, Yannic C / Shin, Sally A / Slein, Matthew D / Heller, Howard M / Kolandaivelu, Kumaran / Middeldorp, Jaap M / Alter, Galit / Julg, Boris

PLoS pathogens

2022 Volume 18, Issue 9, Page(s) e1010738

Abstract: While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses over the course of EBV infection and to gain a better ... ...

Abstract	While Epstein-Barr virus causes mostly asymptomatic infection, associated malignancies, and autoimmune and lymphoproliferative diseases occur. To dissect the evolution of humoral immune responses over the course of EBV infection and to gain a better understanding of the potential contribution of antibody (Ab) function to viral control, we comprehensively profiled Ab specificities and Fc-functionalities using systems serology and VirScan. Ab functions against latent (EBNA1), early (p47/54) and two late (gp350/220 and VCA-p18) EBV proteins were overall modest and/or short-lived, differing from humoral responses induced during acute infection by other viruses such as HIV. In the first year post infection, only p18 elicited robust IgM-driven complement deposition and IgG-driven neutrophil phagocytosis while responses against EBNA-1 were largely Fc-functionally silent and only matured during chronic infection to drive phagocytosis. In contrast, Abs against Influenza virus readily mediated broad Fc-activity in all participants. These data suggest that EBV evades the induction of robust Fc-functional Abs, potentially due to the virus' life cycle, switching from lytic to latent stages during infection.
MeSH term(s)	Antibodies, Viral ; Epstein-Barr Virus Infections ; Epstein-Barr Virus Nuclear Antigens ; Herpesvirus 4, Human ; Humans ; Immunoglobulin G ; Immunoglobulin M
Chemical Substances	Antibodies, Viral ; Epstein-Barr Virus Nuclear Antigens ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2022-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010738
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Article ; Online: Differential Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Profiles After Allergic Reactions to Messenger RNA Coronavirus Disease 2019 Vaccine.

Maron, Jenny S / Conroy, Michelle / Naranbai, Vivek / Samarakoon, Upeka / Motazedi, Tina / Farmer, Jocelyn R / Freeman, Esther / Banerji, Aleena / Bartsch, Yannic C / Gregory, David J / Poznansky, Mark C / Alter, Galit / Blumenthal, Kimberly G

The Journal of infectious diseases

2022 Volume 226, Issue 7, Page(s) 1231–1236

Abstract: Allergic symptoms after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines occur in up to 2% of recipients. Compared to nonallergic controls (n = 18), individuals with immediate allergic reactions to mRNA COVID-19 vaccines (n = 8) mounted ... ...

Abstract	Allergic symptoms after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines occur in up to 2% of recipients. Compared to nonallergic controls (n = 18), individuals with immediate allergic reactions to mRNA COVID-19 vaccines (n = 8) mounted lower immunoglobulin G1 (IgG1) to multiple antigenic targets in severe acute respiratory syndrome coronavirus 2 spike following vaccination, with significantly lower IgG1 to full-length spike (P = .04). Individuals with immediate allergic reactions to mRNA COVID-19 vaccines bound Fcγ receptors similarly to nonallergic controls. Although there was a trend toward an overall reduction in opsonophagocytic function in individuals with immediate allergic reactions compared to nonallergic controls, allergic patients produced functional antibodies exhibiting a high ratio of opsonophagocytic function to IgG1 titer.
MeSH term(s)	2019-nCoV Vaccine mRNA-1273 ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; Hypersensitivity ; Immunity, Humoral ; Immunoglobulin G ; RNA, Messenger ; SARS-CoV-2 ; Vaccination
Chemical Substances	COVID-19 Vaccines ; Immunoglobulin G ; RNA, Messenger ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4)
Language	English
Publishing date	2022-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac107
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Article: Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways.

Lilienthal, Gina-Maria / Rahmöller, Johann / Petry, Janina / Bartsch, Yannic C / Leliavski, Alexei / Ehlers, Marc

Frontiers in immunology

2018 Volume 9, Page(s) 958

Abstract: IgG antibodies (Abs) mediate their effector functions through the interaction with Fcγ receptors (FcγRs) and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This ... ...

Abstract	IgG antibodies (Abs) mediate their effector functions through the interaction with Fcγ receptors (FcγRs) and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q
MeSH term(s)	Animals ; Binding Sites, Antibody ; Complement Activation/drug effects ; Complement C1q/antagonists & inhibitors ; Complement C1q/metabolism ; Complement Pathway, Classical ; Glycosylation ; Hemolysis ; Humans ; Immunoglobulin G/pharmacology ; Mice ; Receptors, IgG/antagonists & inhibitors
Chemical Substances	Immunoglobulin G ; Receptors, IgG ; glycosylated IgG ; Complement C1q (80295-33-6)
Language	English
Publishing date	2018-05-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.00958
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