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  1. Artikel ; Online: Humoral immune responses against SARS-CoV-2 in transplantation: Actionable biomarker or misplaced trust?

    Fishman, Jay A / Alter, Galit

    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

    2022  Band 22, Heft 5, Seite(n) 1291–1292

    Mesh-Begriff(e) Antibodies, Viral ; Biomarkers ; COVID-19 ; Humans ; Immunity, Humoral ; SARS-CoV-2 ; Trust ; Vaccination
    Chemische Substanzen Antibodies, Viral ; Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2022-03-10
    Erscheinungsland United States
    Dokumenttyp Editorial ; Comment
    ZDB-ID 2060594-8
    ISSN 1600-6143 ; 1600-6135
    ISSN (online) 1600-6143
    ISSN 1600-6135
    DOI 10.1111/ajt.17018
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: The next frontier in vaccine design: blending immune correlates of protection into rational vaccine design.

    Britto, Carl / Alter, Galit

    Current opinion in immunology

    2022  Band 78, Seite(n) 102234

    Abstract: Despite the extraordinary speed and success in SARS-Cov-2 vaccine development, the emergence of variants of concern perplexed the vaccine development community. Neutralizing antibodies waned antibodies waned and were evaded by viral variants, despite the ...

    Abstract Despite the extraordinary speed and success in SARS-Cov-2 vaccine development, the emergence of variants of concern perplexed the vaccine development community. Neutralizing antibodies waned antibodies waned and were evaded by viral variants, despite the preservation of protection against severe disease and death across vaccinated populations. Similar to other vaccine design efforts, the lack of mechanistic correlates of immunity against Coronavirus Disease 2019, raised questions related to the need for vaccine redesign and boosting. Hence, our limited understanding of mechanistic correlates of immunity - across pathogens - remains a major obstacle in vaccine development. The identification and incorporation of mechanistic correlates of immunity are key to the accelerated design of highly impactful globally relevant vaccines. Systems-biology tools can be applied strategically to define a complete understanding of mechanistic correlates of immunity. Embedding immunological dissection and target immune profile identification, beyond canonical antibody binding and neutralization, may accelerate the design and success of durable protective vaccines.
    Mesh-Begriff(e) Humans ; Viral Vaccines ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies, Neutralizing ; Antibodies, Viral
    Chemische Substanzen Viral Vaccines ; COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
    Sprache Englisch
    Erscheinungsdatum 2022-08-13
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/j.coi.2022.102234
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Buch: The multi-faceted role of the IgG glycan

    Alter, Galit

    (Immunology Interest Group seminar series)

    2017  

    Abstract: CIT): Immunology Interest Group Seminar Series Beyond their role in pathogen neutralization, antibodies mediate pathogen control and clearance via the recruitment of innate immune effector functions including phagocytosis and cytotoxicity but also via ... ...

    Körperschaft National Institutes of Health (U.S.). / Immunology Interest Group,
    Verfasserangabe Galit Alter
    Serientitel Immunology Interest Group seminar series
    Abstract (CIT): Immunology Interest Group Seminar Series Beyond their role in pathogen neutralization, antibodies mediate pathogen control and clearance via the recruitment of innate immune effector functions including phagocytosis and cytotoxicity but also via the homeostatic regulation of the immune activation. Two modifications to the constant domain of the IgG antibody control this biological activity: 1) the irreversible genomic selection of isotype/subclass and 2) a more subtle alteration in Fc-glycosylation, that together provide instructions to the innate immune system . Because glycosylation alters the affinity of antibodies for Fc-receptors on innate immune cells, mounting evidence suggests that glycosylation may be actively exploited by the immune system to tune antibody biological activity far beyond pathogen control and clearance. While many monoclonal therapeutics have exploited glycosylation, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors is unknown. Two distinct functional roles of antibodies will be discussed in this presentation including the role of antibodies the regulation of the induction of the fhumoral immune response as well as in the regulation of antibody transfer from mother to child. Galit Alter received her PhD in experimental medicine from McGill University, and is currently an Associate Professor in Medicine at Harvard Medical School. Over the past 8 years her research has focused on understanding the role of the innate immune response to chronic viral infections, including HIV and HCV, with a focus on defining the role of Natural Killer (NK) cells in antiviral control. Recently, these studies have shifted gears to begin to define the mechanism by which these innate immune effector cells may be harnessed through vaccination to gain more effective control over viral replication. To do this, her current research interests lie in defining the role of innate immune recruiting antibodies in providing protection from infection. Specifically, she is working towards defining the pathways that result in the targeted production of "protective" antibody glycans to enhance the production of antibodies that can potently block infections. Advancement in understanding how to manipulate the antibody glycan in a targeted manner through vaccination will also lead to the generation of vaccines with broader applications by extending to the improvement of therapeutic vaccines for the treatment of malignancies and autoimmune diseases as well. This knowledge will provide insights into natural antibody glycovariation, and lead to the development of novel approaches to strategically tailor vaccines to induce innate immune cell-recruiting antibodies, with the hope that these findings will ultimately revolutionize the application of vaccines to treat and prevent a remarkably larger range of diseases.
    Mesh-Begriff(e) Immunoglobulin G/immunology ; Antibodies, Viral/immunology ; Immunoglobulin Fc Fragments/immunology ; Glycosylation ; Polysaccharides/immunology ; Antibodies, Neutralizing/immunology
    Sprache Englisch
    Umfang 1 online resource (1 streaming video file (1 hr., 9 min.)) :, color, sound.
    Dokumenttyp Buch
    Anmerkung Closed-captioned.
    Datenquelle Katalog der US National Library of Medicine (NLM)

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  4. Artikel ; Online: The multifaceted roles of breast milk antibodies.

    Atyeo, Caroline / Alter, Galit

    Cell

    2021  Band 184, Heft 6, Seite(n) 1486–1499

    Abstract: Neonates are born with an immature immune system and rely on the transfer of immunity from their mothers. Maternal antibodies are transferred via the placenta and breast milk. Although the role of placentally transferred immunoglobulin G (IgG) is ... ...

    Abstract Neonates are born with an immature immune system and rely on the transfer of immunity from their mothers. Maternal antibodies are transferred via the placenta and breast milk. Although the role of placentally transferred immunoglobulin G (IgG) is established, less is known about the selection of antibodies transferred via breast milk and the mechanisms by which they provide protection against neonatal disease. Evidence suggests that breast milk antibodies play multifaceted roles, preventing infection and supporting the selection of commensals and tolerizing immunity during infancy. Here, we discuss emerging data related to the importance of breast milk antibodies in neonatal immunity and development.
    Mesh-Begriff(e) Animals ; Antibodies/metabolism ; Homeostasis ; Humans ; Immunity ; Immunologic Factors/pharmacology ; Microbiota ; Milk, Human/immunology
    Chemische Substanzen Antibodies ; Immunologic Factors
    Sprache Englisch
    Erscheinungsdatum 2021-03-31
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.02.031
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: The Power of Antibody-Based Surveillance.

    Alter, Galit / Seder, Robert

    The New England journal of medicine

    2020  Band 383, Heft 18, Seite(n) 1782–1784

    Mesh-Begriff(e) Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Iceland ; Immunity, Humoral ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-09-01
    Erscheinungsland United States
    Dokumenttyp Editorial ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMe2028079
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Understanding the role of antibody glycosylation through the lens of severe viral and bacterial diseases.

    Irvine, Edward B / Alter, Galit

    Glycobiology

    2020  Band 30, Heft 4, Seite(n) 241–253

    Abstract: Abundant evidence points to a critical role for antibodies in protection and pathology across infectious diseases. While the antibody variable domain facilitates antibody binding and the blockade of infection, the constant domain (Fc) mediates cross talk ...

    Abstract Abundant evidence points to a critical role for antibodies in protection and pathology across infectious diseases. While the antibody variable domain facilitates antibody binding and the blockade of infection, the constant domain (Fc) mediates cross talk with the innate immune system. The biological activity of the Fc region is controlled genetically via class switch recombination, resulting in the selection of distinct antibody isotypes and subclasses. However, a second modification is made to all antibodies, via post-translational changes in antibody glycosylation. Studies from autoimmunity and oncology have established the role of immunoglobulin G (IgG) Fc glycosylation as a key regulator of humoral immune activity. However, a growing body of literature, exploring IgG Fc glycosylation through the lens of infectious diseases, points to the role of inflammation in shaping Fc-glycan profiles, the remarkable immune plasticity in antibody glycosylation across pathogen-exposed populations, the canonical and noncanonical functions of glycans and the existence of antigen-specific control over antibody Fc glycosylation. Ultimately, this work provides critical new insights into the functional roles for antibody glycosylation as well as lays the foundation for leveraging antibody glycosylation to drive prevention or control across diseases.
    Mesh-Begriff(e) Animals ; Antibodies/immunology ; Bacterial Infections/immunology ; Glycosylation ; Humans ; Immunoglobulin Fc Fragments/immunology ; Polysaccharides/immunology ; Virus Diseases/immunology
    Chemische Substanzen Antibodies ; Immunoglobulin Fc Fragments ; Polysaccharides
    Sprache Englisch
    Erscheinungsdatum 2020-02-26
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1067689-2
    ISSN 1460-2423 ; 0959-6658
    ISSN (online) 1460-2423
    ISSN 0959-6658
    DOI 10.1093/glycob/cwaa018
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Dissecting antibody-mediated protection against SARS-CoV-2.

    Zohar, Tomer / Alter, Galit

    Nature reviews. Immunology

    2020  Band 20, Heft 7, Seite(n) 392–394

    Mesh-Begriff(e) Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity ; Antibody-Dependent Enhancement ; COVID-19 ; COVID-19 Vaccines ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Humans ; Pandemics ; Pneumonia, Viral/immunology ; Viral Vaccines/immunology
    Chemische Substanzen Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Viral Vaccines
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-06-08
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-020-0359-5
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Extra-Neutralizing FcR-Mediated Antibody Functions for a Universal Influenza Vaccine.

    Boudreau, Carolyn M / Alter, Galit

    Frontiers in immunology

    2019  Band 10, Seite(n) 440

    Abstract: While neutralizing antibody titers measured by hemagglutination inhibition have been proposed as a correlate of protection following influenza vaccination, neutralization alone is a modest predictor of protection against seasonal influenza. Instead, ... ...

    Abstract While neutralizing antibody titers measured by hemagglutination inhibition have been proposed as a correlate of protection following influenza vaccination, neutralization alone is a modest predictor of protection against seasonal influenza. Instead, emerging data point to a critical role for additional extra-neutralizing functions of antibodies in protection from infection. Specifically, beyond binding and neutralization, antibodies mediate a variety of additional immune functions via their ability to recruit and deploy innate immune effector function. Along these lines, antibody-dependent cellular cytotoxicity, antibody-mediated macrophage phagocytosis and activation, antibody-driven neutrophil activation, antibody-dependent complement deposition, and non-classical Fc-receptor antibody trafficking have all been implicated in protection from influenza infection. However, the precise mechanism(s) by which the immune system actively tunes antibody functionality to drive protective immunity has been poorly characterized. Here we review the data related to Fc-effector functional protection from influenza and discuss prospects to leverage this humoral immune activity for the development of a universal influenza vaccine.
    Mesh-Begriff(e) Adjuvants, Immunologic ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity ; Complement Activation/immunology ; Epitopes/immunology ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Immunity, Innate ; Immunoglobulin Fab Fragments/immunology ; Immunoglobulin Fc Fragments/immunology ; Immunoglobulin Isotypes/immunology ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Killer Cells, Natural/immunology ; Macrophage Activation/immunology ; Models, Molecular ; Neuraminidase/immunology ; Neutrophil Activation/immunology ; Orthomyxoviridae/immunology ; Phagocytosis ; Protein Processing, Post-Translational ; Receptors, Fc/immunology
    Chemische Substanzen Adjuvants, Immunologic ; Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Immunoglobulin Fab Fragments ; Immunoglobulin Fc Fragments ; Immunoglobulin Isotypes ; Influenza Vaccines ; Receptors, Fc ; Neuraminidase (EC 3.2.1.18)
    Sprache Englisch
    Erscheinungsdatum 2019-03-18
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2019.00440
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Divergent antibody recognition profiles are generated by protective mRNA vaccines against Marburg and Ravn viruses.

    Bukreyev, Alexander / Meyer, Michelle / Gunn, Bronwyn / Pietzsch, Colette / Subramani, Chandru / Saphire, Erica / Crowe, James / Alter, Galit / Himansu, Sunny / Carfi, Andrea

    Research square

    2024  

    Abstract: The first-ever recent Marburg virus (MARV) outbreak in Ghana, West Africa and Equatorial Guinea has refocused efforts towards the development of therapeutics since no vaccine or treatment has been approved. mRNA vaccines were proven successful in a ... ...

    Abstract The first-ever recent Marburg virus (MARV) outbreak in Ghana, West Africa and Equatorial Guinea has refocused efforts towards the development of therapeutics since no vaccine or treatment has been approved. mRNA vaccines were proven successful in a pandemic-response to severe acute respiratory syndrome coronavirus-2, making it an appealing vaccine platform to target highly pathogenic emerging viruses. Here, 1-methyl-pseudouridine-modified mRNA vaccines formulated in lipid nanoparticles (LNP) were developed against MARV and the closely-related Ravn virus (RAVV), which were based on sequences of the glycoproteins (GP) of the two viruses. Vaccination of guinea pigs with both vaccines elicited robust binding and neutralizing antibodies and conferred complete protection against virus replication, disease and death. The study characterized antibody responses to identify disparities in the binding and functional profiles between the two viruses and regions in GP that are broadly reactive. For the first time, the glycan cap is highlighted as an immunoreactive site for marburgviruses, inducing both binding and neutralizing antibody responses that are dependent on the virus. Profiling the antibody responses against the two viruses provided an insight into how antigenic differences may affect the response towards conserved GP regions which would otherwise be predicted to be cross-reactive and has implications for the future design of broadly protective vaccines. The results support the use of mRNA-LNPs against pathogens of high consequence.
    Sprache Englisch
    Erscheinungsdatum 2024-03-26
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-4087897/v1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Correlates of protection against SARS-CoV-2 infection and COVID-19 disease.

    Goldblatt, David / Alter, Galit / Crotty, Shane / Plotkin, Stanley A

    Immunological reviews

    2022  Band 310, Heft 1, Seite(n) 6–26

    Abstract: Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS-CoV-2 coronavirus. Measurement of those antibodies by neutralization or binding assays both have predictive value, with binding antibody titers giving the highest ... ...

    Abstract Antibodies against epitopes in S1 give the most accurate CoP against infection by the SARS-CoV-2 coronavirus. Measurement of those antibodies by neutralization or binding assays both have predictive value, with binding antibody titers giving the highest statistical correlation. However, the protective functions of antibodies are multiple. Antibodies with multiple functions other than neutralization influence efficacy. The role of cellular responses can be discerned with respect to CD4
    Mesh-Begriff(e) Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; Epitopes/immunology ; Humans ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology
    Chemische Substanzen Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2022-06-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13091
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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