Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Publication Date: 2011-08-13
    Description: Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516815/" 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/PMC3516815/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Xueling -- Zhou, Tongqing -- Zhu, Jiang -- Zhang, Baoshan -- Georgiev, Ivelin -- Wang, Charlene -- Chen, Xuejun -- Longo, Nancy S -- Louder, Mark -- McKee, Krisha -- O'Dell, Sijy -- Perfetto, Stephen -- Schmidt, Stephen D -- Shi, Wei -- Wu, Lan -- Yang, Yongping -- Yang, Zhi-Yong -- Yang, Zhongjia -- Zhang, Zhenhai -- Bonsignori, Mattia -- Crump, John A -- Kapiga, Saidi H -- Sam, Noel E -- Haynes, Barton F -- Simek, Melissa -- Burton, Dennis R -- Koff, Wayne C -- Doria-Rose, Nicole A -- Connors, Mark -- NISC Comparative Sequencing Program -- Mullikin, James C -- Nabel, Gary J -- Roederer, Mario -- Shapiro, Lawrence -- Kwong, Peter D -- Mascola, John R -- 5U19 AI 067854-06/AI/NIAID NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Sep 16;333(6049):1593-602. doi: 10.1126/science.1207532. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, 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/21835983" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Amino Acid Sequence ; Antibodies, Neutralizing/*chemistry/genetics/*immunology/isolation & purification ; Antibody Affinity ; Antibody Specificity ; Antigens, CD4/metabolism ; Base Sequence ; Binding Sites ; Binding Sites, Antibody ; Complementarity Determining Regions/genetics ; Crystallography, X-Ray ; Epitopes ; *Evolution, Molecular ; Genes, Immunoglobulin Heavy Chain ; HIV Antibodies/*chemistry/genetics/*immunology/isolation & purification ; HIV Envelope Protein gp120/chemistry/*immunology/metabolism ; HIV Infections/immunology ; HIV-1/chemistry/*immunology ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology ; Immunoglobulin Heavy Chains/chemistry/immunology ; Immunoglobulin J-Chains/genetics ; Immunoglobulin Light Chains/chemistry/immunology ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Sequence Analysis, DNA
    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: 2014-03-05
    Description: Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395007/" 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/PMC4395007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Doria-Rose, Nicole A -- Schramm, Chaim A -- Gorman, Jason -- Moore, Penny L -- Bhiman, Jinal N -- DeKosky, Brandon J -- Ernandes, Michael J -- Georgiev, Ivelin S -- Kim, Helen J -- Pancera, Marie -- Staupe, Ryan P -- Altae-Tran, Han R -- Bailer, Robert T -- Crooks, Ema T -- Cupo, Albert -- Druz, Aliaksandr -- Garrett, Nigel J -- Hoi, Kam H -- Kong, Rui -- Louder, Mark K -- Longo, Nancy S -- McKee, Krisha -- Nonyane, Molati -- O'Dell, Sijy -- Roark, Ryan S -- Rudicell, Rebecca S -- Schmidt, Stephen D -- Sheward, Daniel J -- Soto, Cinque -- Wibmer, Constantinos Kurt -- Yang, Yongping -- Zhang, Zhenhai -- NISC Comparative Sequencing Program -- Mullikin, James C -- Binley, James M -- Sanders, Rogier W -- Wilson, Ian A -- Moore, John P -- Ward, Andrew B -- Georgiou, George -- Williamson, Carolyn -- Abdool Karim, Salim S -- Morris, Lynn -- Kwong, Peter D -- Shapiro, Lawrence -- Mascola, John R -- P01 AI082362/AI/NIAID NIH HHS/ -- R01 AI100790/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036. Epub 2014 Mar 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2]. ; 1] Department of Biochemistry, Columbia University, New York, New York 10032, USA [2]. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [4]. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa. ; Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA. ; Torrey Pines Institute, San Diego, California 92037, USA. ; Weill Medical College of Cornell University, New York, New York 10065, USA. ; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa. ; Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA. ; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa. ; Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa. ; Department of Biochemistry, Columbia University, New York, New York 10032, USA. ; 1] NISC Comparative Sequencing program, National Institutes of Health, Bethesda, Maryland 20892, USA [2] NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Medical Microbiology, Academic Medical Center, Amsterdam 1105 AZ, Netherlands. ; 1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [4] Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA. ; 1] Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA [2] Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA [3] Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA. ; 1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa. ; 1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Department of Epidemiology, Columbia University, New York, New York 10032, USA. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa. ; 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Department of Biochemistry, Columbia University, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24590074" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Amino Acid Sequence ; Antibodies, Neutralizing/chemistry/genetics/*immunology/isolation & purification ; Antibody Affinity/genetics/immunology ; Antigens, CD4/immunology/metabolism ; B-Lymphocytes/cytology/immunology/metabolism ; Binding Sites/immunology ; Cell Lineage ; Complementarity Determining Regions/chemistry/genetics/immunology ; Epitope Mapping ; Epitopes, B-Lymphocyte/chemistry/immunology ; Evolution, Molecular ; HIV Antibodies/chemistry/genetics/*immunology/isolation & purification ; HIV Envelope Protein gp160/*chemistry/*immunology ; HIV Infections/immunology ; HIV-1/chemistry/immunology ; Humans ; Models, Molecular ; Molecular Sequence Data ; Neutralization Tests ; Protein Structure, Tertiary ; Somatic Hypermutation, Immunoglobulin/genetics
    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 ...
  • 3
    Publication Date: 2011-11-25
    Description: Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded beta-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406929/" 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/PMC3406929/" 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 -- Pancera, Marie -- Carrico, Chris -- Gorman, Jason -- Julien, Jean-Philippe -- Khayat, Reza -- Louder, Robert -- Pejchal, Robert -- Sastry, Mallika -- Dai, Kaifan -- O'Dell, Sijy -- Patel, Nikita -- Shahzad-ul-Hussan, Syed -- Yang, Yongping -- Zhang, Baoshan -- Zhou, Tongqing -- Zhu, Jiang -- Boyington, Jeffrey C -- Chuang, Gwo-Yu -- Diwanji, Devan -- Georgiev, Ivelin -- Kwon, Young Do -- Lee, Doyung -- Louder, Mark K -- Moquin, Stephanie -- Schmidt, Stephen D -- Yang, Zhi-Yong -- Bonsignori, Mattia -- Crump, John A -- Kapiga, Saidi H -- Sam, Noel E -- Haynes, Barton F -- Burton, Dennis R -- Koff, Wayne C -- Walker, Laura M -- Phogat, Sanjay -- Wyatt, Richard -- Orwenyo, Jared -- Wang, Lai-Xi -- Arthos, James -- Bewley, Carole A -- Mascola, John R -- Nabel, Gary J -- Schief, William R -- Ward, Andrew B -- Wilson, Ian A -- Kwong, Peter D -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- RR017573/RR/NCRR NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Intramural NIH HHS/ -- England -- Nature. 2011 Nov 23;480(7377):336-43. doi: 10.1038/nature10696.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22113616" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/chemistry/immunology ; Amino Acid Motifs ; Amino Acid Sequence ; Antibodies, Neutralizing/chemistry/*immunology ; Antibody Affinity/immunology ; Antibody Specificity/*immunology ; Antigen-Antibody Complex/chemistry/immunology ; Binding Sites, Antibody/immunology ; Conserved Sequence ; Crystallography, X-Ray ; Epitopes/chemistry/immunology ; Glycopeptides/chemistry/immunology ; Glycosylation ; HIV Antibodies/chemistry/*immunology ; HIV Envelope Protein gp120/*chemistry/*immunology ; HIV-1/*chemistry/*immunology ; Hydrogen Bonding ; Immune Evasion ; Models, Molecular ; Molecular Sequence Data ; Polysaccharides/chemistry/immunology ; Protein Structure, Quaternary ; Protein Structure, Tertiary
    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 ...
  • 4
    Publication Date: 2014-08-15
    Description: To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn), whose role in protecting against infection in vivo has not been defined. Here, we show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue localization, which improves protection against lentiviral infection in non-human primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env) protein (denoted VRC01) was modified by site-directed mutagenesis to increase its binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01-LS, displayed increased transcytosis across human FcRn-expressing cellular monolayers in vitro while retaining FcgammaRIIIa binding and function, including antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than VRC01 in non-human primates and persisted in the rectal mucosa even when it was no longer detectable in the serum. Notably, VRC01-LS mediated protection superior to that afforded by VRC01 against intrarectal infection with simian-human immunodeficiency virus (SHIV). These findings suggest that modification of FcRn binding provides a mechanism not only to increase serum half-life but also to enhance mucosal localization that confers immune protection. Mutations that enhance FcRn function could therefore increase the potency and durability of passive immunization strategies to prevent HIV-1 infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433741/" 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/PMC4433741/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ko, Sung-Youl -- Pegu, Amarendra -- Rudicell, Rebecca S -- Yang, Zhi-yong -- Joyce, M Gordon -- Chen, Xuejun -- Wang, Keyun -- Bao, Saran -- Kraemer, Thomas D -- Rath, Timo -- Zeng, Ming -- Schmidt, Stephen D -- Todd, John-Paul -- Penzak, Scott R -- Saunders, Kevin O -- Nason, Martha C -- Haase, Ashley T -- Rao, Srinivas S -- Blumberg, Richard S -- Mascola, John R -- Nabel, Gary J -- DK0034854/DK/NIDDK NIH HHS/ -- DK044319/DK/NIDDK NIH HHS/ -- DK051362/DK/NIDDK NIH HHS/ -- DK053056/DK/NIDDK NIH HHS/ -- DK088199/DK/NIDDK NIH HHS/ -- R01 DK053056/DK/NIDDK NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612. Epub 2014 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA. ; 1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, Maryland 20892-3005, USA [2] Sanofi, 640 Memorial Drive, Cambridge, Massachusetts 02139, USA (R.S.R., Z.-Y.Y. and G.J.N.); Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-8505, USA (M.Z.); University of North Texas System College of Pharmacy, 3500 Camp Bowie Boulevard, RES-340J, Fort Worth, Texas 76107, USA (S.R.P.). ; Division of Gastroenterology, Department of Medicine, Brigham &Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA. ; 1] Department of Microbiology, Medical School, University of Minnesota, 420 Delaware Street South East, Minneapolis, Minnesota 55455, USA [2] Sanofi, 640 Memorial Drive, Cambridge, Massachusetts 02139, USA (R.S.R., Z.-Y.Y. and G.J.N.); Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-8505, USA (M.Z.); University of North Texas System College of Pharmacy, 3500 Camp Bowie Boulevard, RES-340J, Fort Worth, Texas 76107, USA (S.R.P.). ; 1] Clinical Pharmacokinetics Laboratory, Pharmacy Department, Clinical Center, National Institutes of Health, Building 10, 10 Center Drive, Bethesda, Maryland 20814, USA [2] Sanofi, 640 Memorial Drive, Cambridge, Massachusetts 02139, USA (R.S.R., Z.-Y.Y. and G.J.N.); Center for Genetics of Host Defense, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-8505, USA (M.Z.); University of North Texas System College of Pharmacy, 3500 Camp Bowie Boulevard, RES-340J, Fort Worth, Texas 76107, USA (S.R.P.). ; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6700A Rockledge Drive, Room 5235, Bethesda, Maryland 20892, USA. ; Department of Microbiology, Medical School, University of Minnesota, 420 Delaware Street South East, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119033" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Rectal ; Animals ; Antibodies, Neutralizing/analysis/blood/genetics/*immunology ; Antibodies, Viral/analysis/blood/genetics/*immunology ; Antibody Affinity/genetics/immunology ; Antibody-Dependent Cell Cytotoxicity/immunology ; Antigens, CD4/metabolism ; Binding Sites/genetics ; Female ; HIV/chemistry/immunology ; HIV Antibodies/analysis/blood/genetics/immunology ; HIV Envelope Protein gp160/chemistry/immunology ; HIV Infections/*immunology/*prevention & control ; Half-Life ; Histocompatibility Antigens Class I/*immunology ; Immunity, Mucosal/immunology ; Immunization, Passive ; Intestinal Mucosa/immunology ; Macaca mulatta ; Male ; Mice ; Mutagenesis, Site-Directed ; Receptors, Fc/*immunology ; Receptors, IgG/immunology/metabolism ; Rectum/immunology ; Simian Acquired Immunodeficiency Syndrome/*immunology/*prevention & control ; Simian Immunodeficiency Virus/immunology ; Transcytosis
    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 ...
  • 5
    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 ...
  • 6
    Publication Date: 2013-12-20
    Description: A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946913/" 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/PMC3946913/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roederer, Mario -- Keele, Brandon F -- Schmidt, Stephen D -- Mason, Rosemarie D -- Welles, Hugh C -- Fischer, Will -- Labranche, Celia -- Foulds, Kathryn E -- Louder, Mark K -- Yang, Zhi-Yong -- Todd, John-Paul M -- Buzby, Adam P -- Mach, Linh V -- Shen, Ling -- Seaton, Kelly E -- Ward, Brandy M -- Bailer, Robert T -- Gottardo, Raphael -- Gu, Wenjuan -- Ferrari, Guido -- Alam, S Munir -- Denny, Thomas N -- Montefiori, David C -- Tomaras, Georgia D -- Korber, Bette T -- Nason, Martha C -- Seder, Robert A -- Koup, Richard A -- Letvin, Norman L -- Rao, Srinivas S -- Nabel, Gary J -- Mascola, John R -- AI100645/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- HHSN27201100016C/PHS HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- Z99 AI999999/Intramural NIH HHS/ -- ZIA AI005019-12/Intramural NIH HHS/ -- England -- Nature. 2014 Jan 23;505(7484):502-8. doi: 10.1038/nature12893. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA. ; SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA. ; 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] George Washington University, Washington DC 20052, USA. ; Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA. ; Department of Surgery, Duke University, Durham, North Carolina 27710, USA. ; 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA. ; Fred Hutchison Cancer Research Center, Seattle, Washington 98109, USA. ; Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA. ; 1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352234" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Disease Susceptibility/immunology ; Female ; Founder Effect ; HIV Antibodies/immunology ; HIV Infections/immunology/*prevention & control/*virology ; HIV-1/chemistry/*immunology ; Humans ; Immune Evasion/immunology ; Macaca mulatta ; Male ; Molecular Sequence Data ; Phylogeny ; Risk ; SAIDS Vaccines/*immunology ; Simian Acquired Immunodeficiency Syndrome/immunology/prevention & ; control/virology ; Simian Immunodeficiency Virus/chemistry/genetics/*immunology/physiology ; env Gene Products, Human Immunodeficiency Virus/immunology
    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 ...
  • 7
    Publication Date: 2016-04-28
    Description: Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively, the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9 - 12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gautam, Rajeev -- Nishimura, Yoshiaki -- Pegu, Amarendra -- Nason, Martha C -- Klein, Florian -- Gazumyan, Anna -- Golijanin, Jovana -- Buckler-White, Alicia -- Sadjadpour, Reza -- Wang, Keyun -- Mankoff, Zachary -- Schmidt, Stephen D -- Lifson, Jeffrey D -- Mascola, John R -- Nussenzweig, Michel C -- Martin, Malcolm A -- AI-100148/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- UM1 AI100663-01/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2016 May 5;533(7601):105-9. doi: 10.1038/nature17677. Epub 2016 Apr 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Microbiology, 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. ; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA. ; Laboratory of Experimental Immunology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. ; Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27120156" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/administration & dosage/immunology ; Animals ; Antibodies, Monoclonal/administration & dosage/blood/genetics/immunology ; Antibodies, Neutralizing/administration & dosage/blood/genetics/immunology ; Female ; HIV Antibodies/*administration & dosage/blood/genetics/*immunology ; HIV Infections/immunology/prevention & control/transmission ; Half-Life ; Immunoglobulin Fc Fragments/chemistry/genetics/immunology ; Macaca mulatta/immunology/virology ; Male ; Mutation/genetics ; Protein Structure, Tertiary ; SAIDS Vaccines/administration & dosage/immunology ; Simian Acquired Immunodeficiency Syndrome/blood/*immunology/*prevention & control ; Simian Immunodeficiency Virus/*immunology ; Time Factors
    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 ...
  • 8
    Publication Date: 2018-07-28
    Description: The therapy for treatment of Mycobacterium tuberculosis infections is long and arduous. It has been hypothesized that the therapy duration is driven primarily by populations of organisms in different metabolic states that replicate slowly or not at all (acid-phase and nonreplicative-persister [NRP]-phase organisms). Linezolid is an oxazolidinone antimicrobial with substantial activity against Log-phase M. tuberculosis . Here, we examined organisms in acid-phase growth and nonreplicative-persister-phenotype growth and determined the effect of differing clinically relevant exposures to linezolid in a hollow-fiber infection model (HFIM). The endpoints measured were bacterial kill over 29 days and whether organisms that were less susceptible to linezolid could be recovered during that period. In addition, we evaluated the effect of administration schedule on linezolid activity, contrasting daily administration with administration of twice the daily dose every other day. Linezolid demonstrated robust activity when administered daily against both acid-phase and NRP-phase organisms. We demonstrated a clear dose response, with 900 mg of linezolid daily generating ≥3 Log(CFU/ml) killing of acid-phase and NRP-phase M. tuberculosis over 29 days. Amplification of a population less susceptible to linezolid was not seen. Activity was reduced with every 48-h dosing, indicating that the minimum concentration ( C min )/MIC ratio drove the microbiological effect. We conclude that once-daily linezolid dosing has substantial activity against M. tuberculosis in acid-phase and NRP-phase metabolic states. Other studies have shown activity against Log-phase M. tuberculosis . Linezolid is a valuable addition to the therapeutic armamentarium for M. tuberculosis and has the potential for substantially shortening therapy duration.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...