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2015, Cell
In a phase I clinical trial, the chimeric hemagglutinin (cHA) immunogen induced antibody responses against the conserved HA stalk domain. However, the landscape of the B cell specificities and subsets induced by this vaccine remain undetermined. Here, we paired single cell RNA-sequencing and B cell receptor repertoire sequencing to analyze the relationship between transcriptome and B cell specificity following cHA immunization. We show that the cHA inactivated vaccine with a squalene-based adjuvant induced a robust activated B cell and memory B cell phenotype against two broadly neutralizing epitopes of the stalk domain. The overall specificities of the acute plasmablast and memory B cell responses were distinct, with the plasmablast compartment largely targeting non-neutralizing epitopes of the HA stalk. Altogether, these data indicate the B cell landscape following cHA vaccination includes diverse B cell subsets that are differentially induced by distinct vaccine formulations, inc...
Frontiers in Immunology
Large-Scale Analysis of B-Cell Epitopes on Influenza Virus Hemagglutinin – Implications for Cross-Reactivity of Neutralizing Antibodies2014 •
Virus Research
Analysis of the vaccine-induced influenza B virus hemagglutinin-specific antibody dependent cellular cytotoxicity response2020 •
2014 •
Proceedings of the National Academy of Sciences
Glycans on influenza hemagglutinin affect receptor binding and immune response2009 •
Recent cases of avian influenza H5N1 and the swine-origin 2009 H1N1 have caused a great concern that a global disaster like the 1918 influenza pandemic may occur again. Viral transmission begins with a critical interaction between hemagglutinin (HA) glycoprotein, which is on the viral coat of influenza, and sialic acid (SA) containing glycans, which are on the host cell surface. To elucidate the role of HA glycosylation in this important interaction, various defined HA glycoforms were prepared, and their binding affinity and specificity were studied by using a synthetic SA microarray. Truncation of the N-glycan structures on HA increased SA binding affinities while decreasing specificity toward disparate SA ligands. The contribution of each monosaccharide and sulfate group within SA ligand structures to HA binding energy was quantitatively dissected. It was found that the sulfate group adds nearly 100-fold (2.04 kcal/mol) in binding energy to fully glycosylated HA, and so does the b...
Proceedings of the National Academy of Sciences
Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody2012 •
Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines.
Nature Immunology
Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins2017 •
2009 •
2015 •
Antibody (Ab) affinity maturation enables an individual to maintain immunity to an increasing number of pathogens within the limits of a total Ig production threshold. A better understanding of this process is critical for designing vaccines that generate optimal Ab responses to pathogens. Our study describes a simple flow-cytometric method that enumerates virus-specific germinal center (GC) B cells as well as their AC50, a measure of Ab avidity, defined as the antigen concentration required to detect 50% of specific B cells. Using a model of mouse Ab responses to the influenza A virus hemagglutinin (IAV HA), we obtained data indicating that AC50 decreases with time postinfection in an affinity maturation-dependent process. As proof of principle of the utility of the method, our data clearly show that relative to intranasal IAV infection, intramuscular immunization against inactivated IAV in adjuvant results in a diminished GC HA B cell response, with increased AC50 correlating with...
Discrete Dynamics in Nature and Society
Analytical Solutions for Systems of Singular Partial Differential-Algebraic Equations2015 •
Revista Brasileira de Medicina do Esporte
Análise de um ciclone semi-estacionário na costa sul do Brasil associado a bloqueio atmosférico2009 •
Revista Medica De Risaralda
SIDA y sus complicaciones2003 •
2009 •
Croatian Medical Journal
Expression and possible prognostic role of MAGE-A4, NY-ESO-1, and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study2006 •
Clinical and Translational Allergy
Omalizumab: clinical use for the treatment of an adolescent with difficult asthma2013 •
„Biuletyn IPN”, nr 6
„Black Thursday Bread Riots”. Reakcje brytyjskiej prasy na Poznański Czerwiec, „Biuletyn IPN” 2021, nr 6.2021 •
arXiv: Quantum Physics
Local and nonlocal probabilistic cloning of qubit states via partially entangled twin photons2016 •
2019 •
Politische Vierteljahresschrift
Sammelbesprechung: Demokratie in Ostasien2004 •
Research in Microbiology
Biochemical characterization of the glucose kinase from Streptomyces coelicolor compared to Streptomyces peucetius var. caesius2005 •
PLoS Neglected Tropical Diseases
Cultivation-Independent Methods Reveal Differences among Bacterial Gut Microbiota in Triatomine Vectors of Chagas Disease2012 •
Data and Information Management
The Geopolitical and Socioeconomic Factors of Digitization in Vietnam: Technology Adoption in the Art and Cultural Sector During the Covid-19 Pandemic2021 •
Annals of Behavioral Medicine
Explanatory Model for Asthma Disparities in Latino Children: Results from the Latino Childhood Asthma Project2019 •
Journal of Research on Technology in Education
Mathematics and At-Risk Adult Learners2005 •
2015 •
Multidisciplinary Reviews
Comparative analysis of critical infrastructure and public significance enterprises2024 •
Physics Procedia
Negative Curvature Hollow-core Fibers: Dispersion Properties and Femtosecond Pulse Delivery2015 •
European Journal of Engineering Education
Scholarship of teaching and learning: ‘what the hell’ are we getting ourselves into?2016 •
American journal of infection control
Fecal carriage of carbapenem-resistant Enterobacteriaceae in a Chinese university hospital2014 •