Defining B cell immunodominance to viruses
Davide Angeletti,James S. Gibbs,Matthew Angel,Ivan Kosik,Heather D. Hickman,Gregory M. Frank,Suman R. Das,Suman R. Das,Adam K. Wheatley,Madhu Prabhakaran,David J. Leggat,Adrian B. McDermott,Jonathan W. Yewdell +12 more
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This study shows that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain.Abstract:
Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.read more
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The human antibody response to influenza A virus infection and vaccination.
TL;DR: The differences between natural infection and vaccination in terms of the antibody responses they induce and how these responses protect against future infection are reviewed.
Journal ArticleDOI
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.
Allison J. Greaney,Tyler N. Starr,Tyler N. Starr,Christopher O. Barnes,Yiska Weisblum,Fabian Schmidt,Marina Caskey,Christian Gaebler,Alice Cho,Marianna Agudelo,Shlomo Finkin,Zijun Wang,Daniel Poston,Frauke Muecksch,Theodora Hatziioannou,Paul D. Bieniasz,Davide F. Robbiani,Davide F. Robbiani,Michel C. Nussenzweig,Michel C. Nussenzweig,Pamela J. Bjorkman,Jesse D. Bloom,Jesse D. Bloom +22 more
TL;DR: This article used a yeast display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures.
Journal ArticleDOI
Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance
Kimberly M. Cirelli,Kimberly M. Cirelli,Diane G. Carnathan,Diane G. Carnathan,Diane G. Carnathan,Bartek Nogal,Jacob T. Martin,Jacob T. Martin,Oscar L. Rodriguez,Amit A. Upadhyay,Chiamaka A. Enemuo,Chiamaka A. Enemuo,Etse H. Gebru,Etse H. Gebru,Yury Choe,Yury Choe,Federico Viviano,Federico Viviano,Catherine Nakao,Matthias Pauthner,Samantha M. Reiss,Samantha M. Reiss,Christopher A. Cottrell,Melissa Smith,Raiza Bastidas,William S. Gibson,Amber N. Wolabaugh,Mariane B. Melo,Mariane B. Melo,Benjamin Cossette,Venkatesh Kumar,Nirav B. Patel,Talar Tokatlian,Talar Tokatlian,Sergey Menis,Daniel W. Kulp,Daniel W. Kulp,Dennis R. Burton,Dennis R. Burton,Ben Murrell,Ben Murrell,William R. Schief,William R. Schief,Steven E. Bosinger,Andrew B. Ward,Corey T. Watson,Guido Silvestri,Guido Silvestri,Guido Silvestri,Darrell J. Irvine,Shane Crotty,Shane Crotty,Shane Crotty +52 more
TL;DR: It is found that two independent methods of slow delivery immunization of rhesus monkeys resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates.
Journal ArticleDOI
Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice.
Alexander A. Cohen,Priyanthi N. P. Gnanapragasam,Yu E. Lee,Pauline R. Hoffman,Susan Ou,Leesa M. Kakutani,Jennifer R. Keeffe,Hung-Jen Wu,Mark Howarth,Anthony P. West,Christopher O. Barnes,Michel C. Nussenzweig,Pamela J. Bjorkman +12 more
TL;DR: In this article, a single immunization with mosaic RBD nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.
Journal ArticleDOI
Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
Robert K. Abbott,Jeong Hyun Lee,Jeong Hyun Lee,Sergey Menis,Patrick Skog,Meghan Rossi,Meghan Rossi,Takayuki Ota,Daniel W. Kulp,Deepika Bhullar,Oleksandr Kalyuzhniy,Colin Havenar-Daughton,Colin Havenar-Daughton,William R. Schief,David Nemazee,Shane Crotty,Shane Crotty,Shane Crotty +17 more
TL;DR: The data reveal dominant influences of precursor frequency, affinity, and avidity for interclonal GC competition and indicate that germline‐targeting immunogens can overcome these challenges with high‐affinity multimeric designs.
References
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The Collaborative Cross, a community resource for the genetic analysis of complex traits
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TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Journal ArticleDOI
The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype).
TL;DR: An operational antigenic map of the hemagglutinin of influenza virus A/PR/8/34 indicates the presence of five immunodominant antigenic regions exhibiting various degrees of operational linkage.
Journal ArticleDOI
The structure and receptor binding properties of the 1918 influenza hemagglutinin.
Steven J. Gamblin,Lesley F. Haire,Rupert J. Russell,D.J. Stevens,Bing Xiao,Y. Ha,N. Vasisht,David A. Steinhauer,Rod S. Daniels,Alex J. Elliot,Don C. Wiley,John J. Skehel +11 more
TL;DR: The crystal structures of the HA from the 1918 virus and two closelyrelated HAs in complex with receptor analogs are determined, explaining how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how the virus was able to spread in the human population.
Journal ArticleDOI
Computational design of proteins targeting the conserved stem region of influenza hemagglutinin.
Sarel J. Fleishman,Timothy A. Whitehead,Damian C. Ekiert,C. Dreyfus,Jacob E. Corn,Eva-Maria Strauch,Ian A. Wilson,David Baker +7 more
TL;DR: In this paper, a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule was described, and two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity.
Journal ArticleDOI
Disquisitions on original antigenic sin : i. evidence in man
TL;DR: The basic difference between primary and secondary reactivity rests on the presence of a trapping mechanism that allows anamnestic production of antibody against lower doses of the homologous antigen, thus preventing a standard primary response and allowing manifestations of Original Antigenic Sin.
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