Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2013-11-02
    Description: Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site O, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site O when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site O-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461862/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461862/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLellan, Jason S -- Chen, Man -- Joyce, M Gordon -- Sastry, Mallika -- Stewart-Jones, Guillaume B E -- Yang, Yongping -- Zhang, Baoshan -- Chen, Lei -- Srivatsan, Sanjay -- Zheng, Anqi -- Zhou, Tongqing -- Graepel, Kevin W -- Kumar, Azad -- Moin, Syed -- Boyington, Jeffrey C -- Chuang, Gwo-Yu -- Soto, Cinque -- Baxa, Ulrich -- Bakker, Arjen Q -- Spits, Hergen -- Beaumont, Tim -- Zheng, Zizheng -- Xia, Ningshao -- Ko, Sung-Youl -- Todd, John-Paul -- Rao, Srinivas -- Graham, Barney S -- Kwong, Peter D -- ZIA AI005024-11/Intramural NIH HHS/ -- ZIA AI005061-10/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Nov 1;342(6158):592-8. doi: 10.1126/science.1243283.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24179220" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/immunology ; Antigens, Viral/*chemistry/genetics/immunology ; Crystallography, X-Ray ; Cysteine/chemistry/genetics ; Glycoproteins/*chemistry/genetics/immunology ; Humans ; Macaca ; Mice ; Protein Engineering ; Protein Multimerization ; Protein Stability ; Protein Structure, Tertiary ; Respiratory Syncytial Virus Infections/*prevention & control ; Respiratory Syncytial Virus Vaccines/*chemistry ; Vaccination ; Viral Fusion Proteins/*chemistry/genetics/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2013-05-11
    Description: Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1-neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined "neutralization fingerprints" for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1-infected donors and a chimeric siman-human immunodeficiency virus-infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Georgiev, Ivelin S -- Doria-Rose, Nicole A -- Zhou, Tongqing -- Kwon, Young Do -- Staupe, Ryan P -- Moquin, Stephanie -- Chuang, Gwo-Yu -- Louder, Mark K -- Schmidt, Stephen D -- Altae-Tran, Han R -- Bailer, Robert T -- McKee, Krisha -- Nason, Martha -- O'Dell, Sijy -- Ofek, Gilad -- Pancera, Marie -- Srivatsan, Sanjay -- Shapiro, Lawrence -- Connors, Mark -- Migueles, Stephen A -- Morris, Lynn -- Nishimura, Yoshiaki -- Martin, Malcolm A -- Mascola, John R -- Kwong, Peter D -- U19 AI51794/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 May 10;340(6133):751-6. doi: 10.1126/science.1233989.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23661761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Neutralizing/blood/*immunology ; Epitope Mapping ; HIV Antibodies/blood/*immunology ; HIV Infections/blood/*immunology ; HIV-1/*immunology/isolation & purification ; Humans ; Immunodominant Epitopes/chemistry/immunology ; Macaca ; Neutralization Tests ; Protein Conformation ; Serum/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2014-09-05
    Description: The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) 〈50 mug ml(-1). The median IC50 of neutralized viruses was 0.033 mug ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224615/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224615/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Jinghe -- Kang, Byong H -- Pancera, Marie -- Lee, Jeong Hyun -- Tong, Tommy -- Feng, Yu -- Imamichi, Hiromi -- Georgiev, Ivelin S -- Chuang, Gwo-Yu -- Druz, Aliaksandr -- Doria-Rose, Nicole A -- Laub, Leo -- Sliepen, Kwinten -- van Gils, Marit J -- de la Pena, Alba Torrents -- Derking, Ronald -- Klasse, Per-Johan -- Migueles, Stephen A -- Bailer, Robert T -- Alam, Munir -- Pugach, Pavel -- Haynes, Barton F -- Wyatt, Richard T -- Sanders, Rogier W -- Binley, James M -- Ward, Andrew B -- Mascola, John R -- Kwong, Peter D -- Connors, Mark -- 280829/European Research Council/International -- AI84714/AI/NIAID NIH HHS/ -- AI93278/AI/NIAID NIH HHS/ -- P01 AI082362/AI/NIAID NIH HHS/ -- R01 AI100790/AI/NIAID NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- ZIA AI000855-15/Intramural NIH HHS/ -- ZIA AI001090-05/Intramural NIH HHS/ -- England -- Nature. 2014 Nov 6;515(7525):138-42. doi: 10.1038/nature13601. Epub 2014 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] The Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [2] International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; San Diego Biomedical Research Institute, San Diego, California 92121, USA. ; International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands. ; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA. ; Duke Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA. ; 1] Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam 1100 DD, The Netherlands [2] Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186731" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Antibodies, Monoclonal/chemistry/genetics/immunology/pharmacology ; Antibodies, Neutralizing/chemistry/genetics/*immunology/pharmacology ; *Antibody Affinity ; Antibody Specificity ; Antigens, CD4/metabolism ; Cell Line ; Cell Membrane/virology ; Conserved Sequence ; Epitope Mapping ; Epitopes/chemistry/immunology ; HIV Antibodies/chemistry/genetics/*immunology/pharmacology ; HIV Envelope Protein gp120/*chemistry/*immunology ; HIV Envelope Protein gp41/*chemistry/*immunology ; HIV-1/drug effects/immunology ; Humans ; Immunoglobulin Fab Fragments/chemistry/genetics/immunology/ultrastructure ; Inhibitory Concentration 50 ; Leukocytes, Mononuclear ; Models, Molecular ; Molecular Sequence Data ; Receptors, CCR5/metabolism ; Virus Internalization/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...