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Article ; Online: Deciphering Fc-effector functions against SARS-CoV-2.

Beaudoin-Bussières, Guillaume / Finzi, Andrés

2024

Abstract: Major efforts were deployed to study the antibody response against SARS-CoV-2. Antibodies neutralizing SARS-CoV-2 have been extensively studied in the context of infections, vaccinations, and breakthrough infections. Antibodies, however, are pleiotropic ... ...

Abstract	Major efforts were deployed to study the antibody response against SARS-CoV-2. Antibodies neutralizing SARS-CoV-2 have been extensively studied in the context of infections, vaccinations, and breakthrough infections. Antibodies, however, are pleiotropic proteins that have many functions in addition to neutralization. These include Fc-effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Although important to combat viral infections, these Fc-effector functions were less studied in the context of SARS-CoV-2 compared with binding and neutralization. This is partly due to the difficulty in developing reliable assays to measure Fc-effector functions compared to antibody binding and neutralization. Multiple assays have now been developed and can be used to measure different Fc-effector functions. Here, we review these assays and what is known regarding anti-SARS-CoV-2 Fc-effector functions. Overall, this review summarizes and updates our current state of knowledge regarding anti-SARS-CoV-2 Fc-effector functions.
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/j.tim.2024.01.005
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Article ; Online: A new flow cytometry assay to measure antibody-dependent cellular cytotoxicity against SARS-CoV-2 Spike-expressing cells.

Beaudoin-Bussières, Guillaume / Richard, Jonathan / Prévost, Jérémie / Goyette, Guillaume / Finzi, Andrés

STAR protocols

2021 Volume 2, Issue 4, Page(s) 100851

Abstract: Antibodies can engage specific receptors at the surface of effector cells and mediate several functions beyond viral neutralization. Increasing evidence suggests that Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), ...

Abstract	Antibodies can engage specific receptors at the surface of effector cells and mediate several functions beyond viral neutralization. Increasing evidence suggests that Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), have an important role in protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We engineered a cell line stably expressing a GFP-tagged SARS-CoV-2 spike to measure ADCC. This protocol provides an optimized way of measuring ADCC activity mediated by anti-SARS-CoV-2 Spike monoclonal antibodies or plasma from previously infected or vaccinated individuals. For complete details on the use and execution of this protocol, please refer to Anand et al. (2021b).
MeSH term(s)	Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; Flow Cytometry/methods ; Humans ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2021-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2021.100851
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A new flow cytometry assay to measure antibody-dependent cellular cytotoxicity against SARS-CoV-2 Spike-expressing cells

Guillaume Beaudoin-Bussières / Jonathan Richard / Jérémie Prévost / Guillaume Goyette / Andrés Finzi

STAR Protocols, Vol 2, Iss 4, Pp 100851- (2021)

2021

Abstract: Summary: Antibodies can engage specific receptors at the surface of effector cells and mediate several functions beyond viral neutralization. Increasing evidence suggests that Fc-mediated effector functions, such as antibody-dependent cellular ... ...

Abstract	Summary: Antibodies can engage specific receptors at the surface of effector cells and mediate several functions beyond viral neutralization. Increasing evidence suggests that Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), have an important role in protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We engineered a cell line stably expressing a GFP-tagged SARS-CoV-2 spike to measure ADCC. This protocol provides an optimized way of measuring ADCC activity mediated by anti-SARS-CoV-2 Spike monoclonal antibodies or plasma from previously infected or vaccinated individuals.For complete details on the use and execution of this protocol, please refer to Anand et al. (2021b).
Keywords	Immunology ; Microbiology ; Science (General) ; Q1-390
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Recent SARS-CoV-2 Infection Enhances Antibody-Dependent Cellular Cytotoxicity against Several Omicron Subvariants following a Fourth mRNA Vaccine Dose.

Beaudoin-Bussières, Guillaume / Tauzin, Alexandra / Dionne, Katrina / Gendron-Lepage, Gabrielle / Medjahed, Halima / Perreault, Josée / Levade, Inès / Alfadhli, Laila / Bo, Yuxia / Bazin, Renée / Côté, Marceline / Finzi, Andrés

Viruses

2023 Volume 15, Issue 6

Abstract: Since the beginning of the SARS-CoV-2 pandemic, several variants of concern (VOCs), such as the Alpha, Beta, Gamma, Delta and Omicron variants, have arisen and spread worldwide. Today, the predominant circulating subvariants are sublineages of the ... ...

Abstract	Since the beginning of the SARS-CoV-2 pandemic, several variants of concern (VOCs), such as the Alpha, Beta, Gamma, Delta and Omicron variants, have arisen and spread worldwide. Today, the predominant circulating subvariants are sublineages of the Omicron variant, which have more than 30 mutations in their Spike glycoprotein compared to the ancestral strain. The Omicron subvariants were significantly less recognized and neutralized by antibodies from vaccinated individuals. This resulted in a surge in the number of infections, and booster shots were recommended to improve responses against these variants. While most studies mainly measured the neutralizing activity against variants, we and others previously reported that Fc-effector functions, including antibody-dependent cellular cytotoxicity (ADCC), play an important role in humoral responses against SARS-CoV-2. In this study, we analyzed Spike recognition and ADCC activity against several Omicron subvariants by generating cell lines expressing different Omicron subvariant Spikes. We tested these responses in a cohort of donors, who were recently infected or not, before and after a fourth dose of mRNA vaccine. We showed that ADCC activity is less affected than neutralization by the antigenic shift of the tested Omicron subvariant Spikes. Moreover, we found that individuals with a history of recent infection have higher antibody binding and ADCC activity against all Omicron subvariants than people who were not recently infected. With an increase in the number of reinfections, this study helps better understand Fc-effector responses in the context of hybrid immunity.
MeSH term(s)	Humans ; COVID-19/prevention & control ; SARS-CoV-2/genetics ; Antibody-Dependent Cell Cytotoxicity ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; Antibodies, Viral ; mRNA Vaccines
Chemical Substances	Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; Antibodies, Viral ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-05-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15061274
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity

Beaudoin-Bussières, Guillaume / Arduini, Ariana / Bourassa, Catherine / Medjahed, Halima / Gendron-Lepage, Gabrielle / Richard, Jonathan / Pan, Qinghua / Wang, Zhen / Liang, Zhen / Finzi, Andrés

Viruses. 2022 June 07, v. 14, no. 6

2022

Abstract: Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps ... ...

Abstract	Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.
Keywords	CD8-positive T-lymphocytes ; Severe acute respiratory syndrome coronavirus 2 ; cytotoxicity ; immune evasion ; monocytes
Language	English
Dates of publication	2022-0607
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061237
Database	NAL-Catalogue (AGRICOLA)

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Article: Effects of gp120 Inner Domain (ID2) Immunogen Doses on Elicitation of Anti-HIV-1 Functional Fc-Effector Response to C1/C2 (Cluster A) Epitopes in Mice.

Sherburn, Rebekah / Tolbert, William D / Gottumukkala, Suneetha / Beaudoin-Bussières, Guillaume / Finzi, Andrés / Pazgier, Marzena

Microorganisms

2020 Volume 8, Issue 10

Abstract: Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) ... ...

Abstract	Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) epitopes within the gp120 constant 1 and 2 regions (C1/C2 or Cluster A epitopes). However, recent passive immunization studies have not been able to definitively confirm roles for these antibodies in HIV-1 prevention mostly due to the complications of cross-species Fc-FcR interactions and suboptimal dosing strategies. Here, we use our stabilized gp120 Inner domain (ID2) immunogen that displays the Cluster A epitopes within a minimal structural unit of HIV-1 Env to investigate an immunization protocol that induces a fine-tuned antibody repertoire capable of an effective Fc-effector response. This includes the generation of isotypes and the enhanced antibody specificity known to be vital for maximal Fc-effector activities, while minimizing the induction of isotypes know to be detrimental for these functions. Although our studies were done in in BALB/c mice we conclude that when optimally titrated for the species of interest, ID2 with GLA-SE adjuvant will elicit high titers of antibodies targeting the Cluster A region with potent Fc-mediated effector functions, making it a valuable immunogen candidate for testing an exclusive role of non-neutralizing antibody response in HIV-1 protection in vaccine settings.
Language	English
Publishing date	2020-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms8101490
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Article ; Online: Intra-Host Evolution Analyses in an Immunosuppressed Patient Supports SARS-CoV-2 Viral Reservoir Hypothesis.

Viruses

2024 Volume 16, Issue 3

Abstract: Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore ... ...

Abstract	Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein's receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we present the case of an immunosuppressed patient that developed distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. These mutations were acquired without the patient being treated with mAbs nor convalescent sera and without them developing a detectable immune response to the virus. We also provide additional evidence for a viral reservoir based on intra-host phylogenetics, which led to a viral substrain that evolved elsewhere in the patient's body, colonizing their upper respiratory tract (URT). The presence of SARS-CoV-2 viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable, and potential explanations for long-COVID cases.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; Post-Acute COVID-19 Syndrome ; COVID-19 ; COVID-19 Serotherapy ; Immunocompromised Host ; Antibodies, Monoclonal ; Mutation ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Monoclonal ; Spike Glycoprotein, Coronavirus ; Antibodies, Viral ; Antibodies, Neutralizing ; spike protein, SARS-CoV-2
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030342
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Small CD4 mimetics sensitize HIV-1-infected macrophages to antibody-dependent cellular cytotoxicity.

Laumaea, Annemarie / Marchitto, Lorie / Ding, Shilei / Beaudoin-Bussières, Guillaume / Prévost, Jérémie / Gasser, Romain / Chatterjee, Debashree / Gendron-Lepage, Gabrielle / Medjahed, Halima / Chen, Hung-Ching / Smith, Amos B / Ding, Haitao / Kappes, John C / Hahn, Beatrice H / Kirchhoff, Frank / Richard, Jonathan / Duerr, Ralf / Finzi, Andrés

Cell reports

2023 Volume 42, Issue 1, Page(s) 111983

Abstract: HIV-1 envelope (Env) conformation determines the susceptibility of infected ... ...

Abstract	HIV-1 envelope (Env) conformation determines the susceptibility of infected CD4
MeSH term(s)	Humans ; HIV Infections/metabolism ; CD4-Positive T-Lymphocytes ; HIV-1 ; env Gene Products, Human Immunodeficiency Virus/metabolism ; HIV Seropositivity ; HIV Antibodies/metabolism ; Epitopes/metabolism ; Antibody-Dependent Cell Cytotoxicity
Chemical Substances	env Gene Products, Human Immunodeficiency Virus ; HIV Antibodies ; Epitopes
Language	English
Publishing date	2023-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111983
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Article: Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers.

Stoddard, Caitlin I / Sung, Kevin / Yaffe, Zak A / Weight, Haidyn / Beaudoin-Bussières, Guillaume / Galloway, Jared / Gantt, Soren / Adhiambo, Judith / Begnel, Emily R / Ojee, Ednah / Slyker, Jennifer / Wamalwa, Dalton / Kinuthia, John / Finzi, Andrés / Matsen, Frederick A / Lehman, Dara A / Overbaugh, Julie

bioRxiv : the preprint server for biology

2023

Abstract: Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and ... ...

Abstract	Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody repertoires and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.06.527330
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Article ; Online: Humoral Responses Elicited after a Fifth Dose of SARS-CoV-2 mRNA Bivalent Vaccine.

Tauzin, Alexandra / Beaudoin-Bussières, Guillaume / Benlarbi, Mehdi / Nayrac, Manon / Bo, Yuxia / Gendron-Lepage, Gabrielle / Medjahed, Halima / Perreault, Josée / Gokool, Laurie / Arlotto, Pascale / Morrisseau, Chantal / Tremblay, Cécile / Kaufmann, Daniel E / Martel-Laferrière, Valérie / Levade, Inès / Côté, Marceline / Bazin, Renée / Finzi, Andrés

Viruses

2023 Volume 15, Issue 9

Abstract: While an important part of the world's population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize ... ...

Abstract	While an important part of the world's population is vaccinated against SARS-CoV-2, new variants continue to emerge. We observe that even after a fifth dose of the mRNA bivalent vaccine, most vaccinated individuals have antibodies that poorly neutralize several Omicron subvariants, including BQ.1.1, XBB, XBB.1.5, FD.1.1, and CH.1.1. However, Fc-effector functions remain strong and stable over time against new variants, which may partially explain why vaccines continue to be effective. We also observe that donors who have been recently infected have stronger antibody functional activities, including neutralization and Fc-effector functions, supporting the observations that hybrid immunity leads to better humoral responses.
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; COVID-19/prevention & control ; Antibodies ; Vaccines, Combined ; RNA, Messenger/genetics
Chemical Substances	Antibodies ; Vaccines, Combined ; RNA, Messenger
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15091926
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