7 results on '"Masaru Kanekiyo"'
Search Results
2. Co-immunization with hemagglutinin stem immunogens elicits cross-group neutralizing antibodies and broad protection against influenza A viruses
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Syed M. Moin, Jeffrey C. Boyington, Seyhan Boyoglu-Barnum, Rebecca A. Gillespie, Gabriele Cerutti, Crystal Sao-Fong Cheung, Alberto Cagigi, John R. Gallagher, Joshua Brand, Madhu Prabhakaran, Yaroslav Tsybovsky, Tyler Stephens, Brian E. Fisher, Adrian Creanga, Sila Ataca, Reda Rawi, Kizzmekia S. Corbett, Michelle C. Crank, Gunilla B. Karlsson Hedestam, Jason Gorman, Adrian B. McDermott, Audray K. Harris, Tongqing Zhou, Peter D. Kwong, Lawrence Shapiro, John R. Mascola, Barney S. Graham, and Masaru Kanekiyo
- Subjects
Influenza A Virus, H5N1 Subtype ,Immunology ,Ferrets ,Hemagglutinin Glycoproteins, Influenza Virus ,Influenza A Virus, H7N9 Subtype ,Antibodies, Viral ,Antibodies, Neutralizing ,Mice ,Hemagglutinins ,Infectious Diseases ,Orthomyxoviridae Infections ,Influenza Vaccines ,Influenza, Human ,Animals ,Humans ,Immunology and Allergy ,Immunization ,Broadly Neutralizing Antibodies - Abstract
Current influenza vaccines predominantly induce immunity to the hypervariable hemagglutinin (HA) head, requiring frequent vaccine reformulation. Conversely, the immunosubdominant yet conserved HA stem harbors a supersite that is targeted by broadly neutralizing antibodies (bnAbs), representing a prime target for universal vaccines. Here, we showed that the co-immunization of two HA stem immunogens derived from group 1 and 2 influenza A viruses elicits cross-group protective immunity and neutralizing antibody responses in mice, ferrets, and nonhuman primates (NHPs). Immunized mice were protected from multiple group 1 and 2 viruses, and all animal models showed broad serum-neutralizing activity. A bnAb isolated from an immunized NHP broadly neutralized and protected against diverse viruses, including H5N1 and H7N9. Genetic and structural analyses revealed strong homology between macaque and human bnAbs, illustrating common biophysical constraints for acquiring cross-group specificity. Vaccine elicitation of stem-directed cross-group-protective immunity represents a step toward the development of broadly protective influenza vaccines.
- Published
- 2022
3. Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition
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Wei-Hung Chen, JungHyun Kim, Wei Bu, Nathan L. Board, Yaroslav Tsybovsky, Yanmei Wang, Anna Hostal, Sarah F. Andrews, Rebecca A. Gillespie, Misook Choe, Tyler Stephens, Eun Sung Yang, Amarendra Pegu, Caroline E. Peterson, Brian E. Fisher, John R. Mascola, Stefania Pittaluga, Adrian B. McDermott, Masaru Kanekiyo, M. Gordon Joyce, and Jeffrey I. Cohen
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Mice ,Herpesvirus 4, Human ,Epstein-Barr Virus Infections ,Cricetulus ,Membrane Glycoproteins ,Infectious Diseases ,Viral Envelope Proteins ,Cricetinae ,Immunology ,Animals ,Humans ,Immunology and Allergy ,CHO Cells - Abstract
Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosis and is associated with B cell lymphomas, epithelial cell malignancies, and multiple sclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membrane with host cells and is a target of neutralizing antibodies. Here, we examined the sites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL. We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structural analyses using X-ray crystallography and electron microscopy revealed multiple sites of vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb provided near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model. Our findings provide structural and antigenic knowledge of the viral fusion machinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasize gH/gL as a target for herpesvirus vaccines and therapeutics.
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- 2022
4. Comparison of adjuvants to optimize influenza neutralizing antibody responses
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Jean Haensler, John R. Mascola, Thorsten U. Vogel, Ram Dharanipragada, Michael R. Reardon, Pradeep K. Dhal, Rebecca S. Rudicell, Barney S. Graham, Te-Hui Chou, Daniel Simard, Heather D. Kamp, Kanwen Yang, Joshua M. DiNapoli, Luis Z. Avila, Masaru Kanekiyo, Harry Kleanthous, Marie Garinot, Kurt Swanson, Lingyi Zheng, Xiaochu Duan, Chih-Jen Wei, Shujia Dai, Olivier Bedel, Rebecca A. Gillespie, Magnus Besev, and Gary J. Nabel
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Influenza vaccine ,medicine.medical_treatment ,030231 tropical medicine ,Hemagglutinin (influenza) ,Article ,03 medical and health sciences ,0302 clinical medicine ,Adjuvants, Immunologic ,Immunity ,Evolution of influenza ,Animals ,Humans ,Medicine ,030212 general & internal medicine ,Neutralizing antibody ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Toll-Like Receptors ,Public Health, Environmental and Occupational Health ,virus diseases ,Hemagglutination Inhibition Tests ,Vaccine efficacy ,Antibodies, Neutralizing ,Macaca mulatta ,Vaccination ,HEK293 Cells ,Hemagglutinins ,Infectious Diseases ,Influenza Vaccines ,Immunology ,biology.protein ,Nanoparticles ,Molecular Medicine ,Female ,business ,Adjuvant - Abstract
Seasonal influenza vaccines represent a positive intervention to limit the spread of the virus and protect public health. Yet continual influenza evolution and its ability to evade immunity pose a constant threat. For these reasons, vaccines with improved potency and breadth of protection remain an important need. We previously developed a next-generation influenza vaccine that displays the trimeric influenza hemagglutinin (HA) on a ferritin nanoparticle (NP) to optimize its presentation. Similar to other vaccines, HA-nanoparticle vaccine efficacy is increased by the inclusion of adjuvants during immunization. To identify the optimal adjuvants to enhance influenza immunity, we systematically analyzed TLR agonists for their ability to elicit immune responses. HA-NPs were compatible with nearly all adjuvants tested, including TLR2, TLR4, TLR7/8, and TLR9 agonists, squalene oil-in-water mixtures, and STING agonists. In addition, we chemically conjugated TLR7/8 and TLR9 ligands directly to the HA-ferritin nanoparticle. These TLR agonist-conjugated nanoparticles induced stronger antibody responses than nanoparticles alone, which allowed the use of a 5000-fold-lower dose of adjuvant than traditional admixtures. One candidate, the oil-in-water adjuvant AF03, was also tested in non-human primates and showed strong induction of neutralizing responses against both matched and heterologous H1N1 viruses. These data suggest that AF03, along with certain TLR agonists, enhance strong neutralizing antibody responses following influenza vaccination and may improve the breadth, potency, and ultimately vaccine protection in humans.
- Published
- 2019
5. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses
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Celia Santos, Peter D. Kwong, Wing-Pui Kong, Baoshan Zhang, Yi Zhang, Amy Ransier, Robert T. Bailer, Kwanyee Leung, Richard A. Koup, Sam Darko, Tatsiana Bylund, Sandeep N. Narpala, Hadi M. Yassine, Ulrich Baxa, Cinque Soto, Rebecca A. Gillespie, M. Gordon Joyce, Julie E. Ledgerwood, Xueling Wu, Lawrence Shapiro, Madhu Prabhakaran, Adam K. Wheatley, Ivelin S. Georgiev, Kanta Subbarao, Chen-Hsiang Shen, Adrian B. McDermott, Gwo-Yu Chuang, Yumiko Matsuoka, Mangaiarkarasi Asokan, James C. Mullikin, Yaroslav Tsybovsky, Lingshu Wang, Paul V. Thomas, Jeffrey C. Boyington, Aliaksandr Druz, James R R Whittle, Daniel C. Douek, Eun Sung Yang, Mario Roederer, Masaru Kanekiyo, John R. Mascola, Barney S. Graham, and Christopher R. Lees
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0301 basic medicine ,biology ,Influenza vaccine ,Hemagglutinin (influenza) ,medicine.disease_cause ,Virology ,H5N1 genetic structure ,Influenza ,General Biochemistry, Genetics and Molecular Biology ,Influenza A virus subtype H5N1 ,Epitope ,Vaccination ,03 medical and health sciences ,030104 developmental biology ,Immunization ,biology.protein ,medicine ,Antibody ,Vaccine - Abstract
Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and—in half the subjects—multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies.
- Published
- 2016
6. High-Throughput Mapping of B Cell Receptor Sequences to Antigen Specificity
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Charissa Oosthuysen, Andrea R. Shiakolas, Ivelin S. Georgiev, Priyamvada Acharya, Kelsey A. Pilewski, Rutendo E. Mapengo, Mark Connors, Daniel Lingwood, Ian Setliff, Lynn Morris, Juliana S. Qin, Barney S. Graham, Katarzyna Janowska, Amyn A. Murji, Allison R. Greenplate, Masaru Kanekiyo, Kevin J Kramer, Nagarajan Raju, Larance Ronsard, Simone I. Richardson, and Wyatt J. McDonnell
- Subjects
THP-1 Cells ,B-cell receptor ,Receptors, Antigen, B-Cell ,HIV Antibodies ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Epitopes ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antibody Repertoire ,Antigen ,Humans ,Antigens ,Cells, Cultured ,030304 developmental biology ,Systems immunology ,0303 health sciences ,breakpoint cluster region ,High-Throughput Nucleotide Sequencing ,Sequence Analysis, DNA ,Antibodies, Neutralizing ,Virology ,High-Throughput Screening Assays ,Vaccination ,HEK293 Cells ,biology.protein ,Single-Cell Analysis ,Antibody ,Epitope Mapping ,030217 neurology & neurosurgery - Abstract
B cell receptor (BCR) sequencing is a powerful tool for interrogating immune responses to infection and vaccination, but it provides limited information about the antigen specificity of the sequenced BCRs. Here, we present LIBRA-seq (linking B cell receptor to antigen specificity through sequencing), a technology for high-throughput mapping of paired heavy- and light-chain BCR sequences to their cognate antigen specificities. B cells are mixed with a panel of DNA-barcoded antigens so that both the antigen barcode(s) and BCR sequence are recovered via single-cell next-generation sequencing. Using LIBRA-seq, we mapped the antigen specificity of thousands of B cells from two HIV-infected subjects. The predicted specificities were confirmed for a number of HIV- and influenza-specific antibodies, including known and novel broadly neutralizing antibodies. LIBRA-seq will be an integral tool for antibody discovery and vaccine development efforts against a wide range of antigen targets.
- Published
- 2019
7. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site
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John R. Mascola, Srinivas S. Rao, Takuya Yamamoto, Ulrich Baxa, Barney S. Graham, John Paul Todd, Jeffrey I. Cohen, Richard A. Koup, Michael G. Rossmann, Adrian B. McDermott, Gary J. Nabel, Geng Meng, M. Gordon Joyce, Wei Bu, Masaru Kanekiyo, James R R Whittle, and Sandeep Narpala
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Herpesvirus 4, Human ,Complement receptor 2 ,Herpesvirus Vaccines ,02 engineering and technology ,Crystallography, X-Ray ,Article ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Mice ,03 medical and health sciences ,Immunity ,Viral entry ,medicine ,Animals ,Neutralizing antibody ,030304 developmental biology ,Mice, Inbred BALB C ,0303 health sciences ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Rational design ,Epstein–Barr virus vaccine ,021001 nanoscience & nanotechnology ,Antibodies, Neutralizing ,Virology ,Recombinant Proteins ,3. Good health ,Macaca fascicularis ,Drug Design ,Immunology ,biology.protein ,Nanoparticles ,Female ,Receptors, Complement 3d ,Antibody ,0210 nano-technology ,medicine.drug - Abstract
SummaryEpstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and ∼200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine increased neutralization 10- to 100-fold compared to soluble gp350 by targeting a functionally conserved site of vulnerability, improving vaccine-induced protection in a mouse model. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by arrayed presentation of a conserved viral entry domain, a strategy that can be applied to other viruses.PaperClip
- Published
- 2015
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