Structural Insights into HIV-1 Neutralization by Broadly Neutralizing Antibodies PG9 and PG16
|
|
- Dulcie Jordan
- 5 years ago
- Views:
Transcription
1 Structural Insights into HIV-1 Neutralization by Broadly Neutralizing Antibodies PG9 and PG16 Robert Pejchal, Laura M. Walker, Robyn L. Stanfield, Wayne C. Koff, Sanjay K. Phogat, Pascal Poignard, Dennis R. Burton and Ian A. Wilson Session 05: Novel Monoclonals and Structural Insights AIDS Vaccine 2010, Atlanta Title
2 PG9 and PG16 recognize a V2/V3 epitope on the HIV-1 Env trimer PG9 neutralizes 87% of a panel of 82 viruses (M. Seaman, unpublished data) IC 50 ~< 0.1 ug/ml Novel epitope centered on V1/V2 stem, V2 and V3 (especially for PG16) No structural information for epitope, but can localize near apex of trimer Cryo-ET reconstruction density and modeling based on Liu et al Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, Lehrman JK, Priddy FH, Olsen OA, Frey SM, Hammond PW; Protocol G Principal Investigators, Kaminsky S, Zamb T, Moyle M, Koff WC, Poignard P, Burton DR. (2009) Science 326:285-9 Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target
3 PG16 crystal structure reveals a novel hammerhead subdomain for its 28-residue CDR H3 R. Pejchal, L. M. Walker, R. L. Stanfield, S. K. Phogat, W. C. Koff, P. Poignard, D. R. Burton & I. A. Wilson (2010). PNAS 107: Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1
4 Crystal structure of the antigen-binding fragment (Fab) of antibody PG16 Pancera, M. et al. & P.D. Kwong J. Virol. 84:
5 PG16 crystal structure reveals a novel, sulfated hammerhead subdomain for its 28-residue CDR H3 Hammerhead subdomain protrudes 20Å from combining site Sulfated tyrosine (TyrH100H) provides 10-fold boost in neutralization potency (PG9 hypersulfated) R327A (and bridging sheet residues) knockdown suggests involvement of a CoRbs element R. Pejchal, L. M. Walker, R. L. Stanfield, S. K. Phogat, W. C. Koff, P. Poignard, D. R. Burton & I. A. Wilson (2010). PNAS 107: Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1
6 Structure of 412d with YU2 gp120 (core+v3) Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS, Stanfield RL, Robinson J, Sodroski J, Wilson IA, Wyatt R, Bewley CA, Kwong PD. Science 317: (2007)
7 Variable loop in CDR H3 determines fine specificity of PG9 and PG16 * Tyrosine sandwich stalk stabilizes protrusion of H3 hammerhead 7-residue H3 region varies between PG9 and PG16; forms anti-parallel beta hairpin H3 swap experiment switches PG9 and PG16 neutralization and binding specificity R. Pejchal, L. M. Walker, R. L. Stanfield, S. K. Phogat, W. C. Koff, P. Poignard, D. R. Burton & I. A. Wilson (2010). PNAS 107: Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1
8 Effect of CDR H3 mutation on PG9 neutralization and binding to DU422 gp120 5 Tyr residues in PG9 CDR H3: 100A, 100E, 100G, 100H (sulfated in PG16), and 100K Mutation of 100G and 100H more disruptive than 100A, 100E, and 100K R. Pejchal, L. M. Walker, R. L. Stanfield, S. K. Phogat, W. C. Koff, P. Poignard, D. R. Burton & I. A. Wilson (2010). PNAS 107: Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1
9 Sulfoforms of PG9 CDR H3 Tyr->Phe mutants identified by ESI-MS Purified Tyr->Phe mutants were fractionated by Mono S and eluted fractions were analyzed by ESI- MS Rob Pejchal et al. P04.59 LB Doubly sulfated forms were not detected for 100G and 100H mutants supporting 100G and 100H as natural sulfated sites
10 PG9 homology model Tys H100H Tys H100G Homology model composed of PG9 V L (PDB:3MUH) and PG16 V H (PDB:3MUG) V H V L Tyrosine sulfation based on mass spec data for Tyr->Phe mutants The two sulfated residues are in close proximity Robert Pejchal
11 Revisiting the role of tyrosine sulfation in neutralization potency Co-expression of human tyrosyl protein sulfotransferase promotes hypersulfation (up to quintuple), suggesting all five Tyr in the CDR H3 are capable of being sulfated PG9-S2 achieves optimal neutralization potency >10X higher than hyposulfated forms Rob Pejchal et al. P04.59 LB
12 Sensitivity of PG9 and PG16 neutralization to substitutions eliminating N-linked glycosylation sites * * * N156 and N160 in V1/V2 stem and V2 are important for forming the PG9/16 epitope K. Doores & D. R. Burton (2010). J. Virol, 84: Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16
13 Neutralization activity of MAbs against JR-CSF pseudoviruses using glycosidase inhibitors Expression of trimer in the presence of kifunensine blocks neutralization K. Doores & D. R. Burton (2010). J. Virol, 84: Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16
14 Acknowledgements Wilson Lab Robert Pejchal Yuanzi Hua Dennis Burton Laura Walker Katie Doores Robyn Stanfield IAVI Sanjay Phogat Wayne Koff Peter Kwong, VRC Crystallization Robot Marc Elsliger David Marciano Henry Tien Rob Pejchal et al. P04.59 LB Rob Pejchal et al. P04.59 LB Rob Pejchal et al. P04.59 LB Funding: IAVI, NIH, NIAID NIGMS, Skaggs Institute for Chemical Biology
15 IAVI Neutralizing Antibody Consortium
16 CCR5 N-term binding: results Best Solution Docking energy kcal/mol Priyamvada Acharya Huang CC, Lam SN, A, Bewley CA, Kwong PD, Acharya P, Tang M, Xiang SH, Hussan SS, Stanfield RL, Robinson J, Sodroski J, Wilson IA, Wyatt R, Bewley CA, Kwong PD. Science 317: (2007)
17 CCR5 N-terminus versus 412d Arg 327 STY10 (CCR5) vs STY 104 (412d) STY14 (CCR5) vs STY 107 (412d) Precise chemical mimicry found at energetically important sulfated tyrosine residues: confirmed by mutagenesis
18 Structure of 412d with YU2 gp120 (core+v3) CD4 gp d heavy chain V3 loop Buried STY d light chain Huang CC, Lam SN, A, Bewley CA, Kwong PD, Acharya P, Tang M, Xiang SH, Hussan SS, Stanfield RL, Robinson J, Sodroski J, Wilson IA, Wyatt R, Bewley CA, Kwong PD. Science 317: (2007)
19 Acknowledgements Ian Wilson Rob Pejchal Yuanzi Hua Robyn Stanfield Dennis Burton Laura Walker Katie Doores IAVI NAC Pascal Poignard IAVI Sanjay Phogat Wayne Koff Peter Kwong Funding NIH NIAID IAVI
20 Neutralization of glycan mixed trimer viruses by PG9, PG16, and 2G12 Cells transfected with various proportions of JR-FL E168K (suboptimal) and JR-FL E168K N189A (optimal) show only one optimal monomer is required per trimer to reach maximum neutralization Consistent with previous data demonstrating binding of PG9/16 to a single gp120 monomer K. Doores & D. R. Burton (2010). J. Virol, 84: Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16
21 Neutralization activity of MAbs against 92RW020 and SF162 K160N pseudoviruses when made in the presence of glycosidase inhibitors K. Doores & D. R. Burton (2010). J. Virol, Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16
Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target
Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target Laura M. Walker, 1 * Sanjay K. Phogat, 2 * Po-Ying Chan-Hui, 3 Denise Wagner, 2 Pham Phung, 4 Julie L. Goss,
More informationFrom Antibody to Vaccine a Tale of Structural Biology and Epitope Scaffolds
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services From Antibody to Vaccine a Tale
More informationSupporting Information
Supporting Information Guan et al. 10.1073/pnas.1217609110 Fig. S1. Three patterns of reactivity for CD4-induced (CD4i) mabs. The following representative ELISAs show three patterns of reactivity for CD4i
More informationThe challenge of an HIV vaccine from the antibody perspective. Dennis Burton The Scripps Research Institute
The challenge of an HIV vaccine from the antibody perspective Dennis Burton The Scripps Research Institute AIDS Pandemic Nov 2005 North America 1.2 million [650 000 1.8 million] Caribbean 300 000 [200
More informationBispecific Fusion Antibodies. Exhibit 100% Breadth and Picomolar Potency. Craig Pace, PhD
The Aaron Diamond AIDS Research Center Affiliate of The Rockefeller University Bispecific Fusion Antibodies PG9 Ibalizumab & VRC Ibalizumab Exhibit % Breadth and Picomolar Potency Craig Pace, PhD AIDS
More informationCrystal structure of the neutralizing antibody HK20 in complex with its gp41 antigen
Crystal structure of the neutralizing antibody HK20 in complex with its gp41 antigen David Lutje Hulsik Unit for Virus Host Cell Interaction UMI 3265 University Joseph Fourier-EMBL-CNRS, Grenoble Env catalyzed
More informationImmunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies
JOURNAL OF VIROLOGY, May 2011, p. 4578 4585 Vol. 85, No. 9 0022-538X/11/$12.00 doi:10.1128/jvi.02585-10 Copyright 2011, American Society for Microbiology. All Rights Reserved. Immunotypes of a Quaternary
More informationIdentification of Mutation(s) in. Associated with Neutralization Resistance. Miah Blomquist
Identification of Mutation(s) in the HIV 1 gp41 Subunit Associated with Neutralization Resistance Miah Blomquist What is HIV 1? HIV-1 is an epidemic that affects over 34 million people worldwide. HIV-1
More informationIdentification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth
Article Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth Highlights d CD4bs antibody N6 potently neutralizes 98% of HIV isolates d d N6 potently neutralizes
More informationCrystallization-grade After D After V3 cocktail. Time (s) Time (s) Time (s) Time (s) Time (s) Time (s)
Ligand Type Name 6 Crystallization-grade After 447-52D After V3 cocktail Receptor CD4 Resonance Units 5 1 5 1 5 1 Broadly neutralizing antibodies 2G12 VRC26.9 Resonance Units Resonance Units 3 1 15 1 5
More informationRetrovirology. Open Access RESEARCH
DOI 10.1186/s12977-016-0312-7 Retrovirology RESEARCH Open Access Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen design as it is efficiently cleaved and displays all the broadly
More informationSupplementary Information for. Heavy chain-only IgG2b-llama antibody effects near-pan HIV-1 neutralization by
Supplementary Information for Heavy chain-only IgG2b-llama antibody effects near-pan HIV-1 neutralization by recognizing a CD4-induced epitope that includes elements of co-receptor- and CD4-binding sites
More informationHIV Vaccines: Basic Science
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health HIV Vaccines: Basic Science Richard A. Koup, MD 6 th INTEREST Workshop
More informationAssociation Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies
BASIC AND TRANSLATIONAL SCIENCE Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies Nico Pfeifer, Dr,* Hauke Walter, MD, and Thomas Lengauer, Dr, PhD* Background:
More informationHIV Anti-HIV Neutralizing Antibodies
,**/ The Japanese Society for AIDS Research The Journal of AIDS Research : HIV HIV Anti-HIV Neutralizing Antibodies * Junji SHIBATA and Shuzo MATSUSHITA * Division of Clinical Retrovirology and Infectious
More informationAlternate Antibody-Based Therapeutic Strategies To Purge the HIV Cell Reservoir
Alternate Antibody-Based Therapeutic Strategies To Purge the HIV Cell Reservoir Giuseppe Pantaleo, M.D. Professor of Medicine Head, Division of Immunology and Allergy Executive Director, Swiss Vaccine
More informationNonsynonymous Amino Acid Mutations in gp120 Binding Sites are Related to Progression of HIV-1
Nonsynonymous Amino Acid Mutations in gp120 Binding Sites are Related to Progression of HIV-1 Matthew Allegretti and Anindita Varshneya BIOL 368: Bioinformatics Laboratory Loyola Marymount University November
More informationComputational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data The MIT Faculty has made this article openly available. Please share how this access benefits
More informationSpike Trimer RNA. dsdna
Spike Trimer RNA dsdna Spike Trimer RNA Spike trimer subunits xxx gp120: receptor and coreceptor binding xxxxxxx gp41: membrane anchoring and target cell fusion dsdna Spike Trimer HIV gp120 binds to host
More informationSupporting Information
Supporting Information Walker et al. 1.173/pnas.111753118 - JR-CSF 1 3 1 4 1 5 1 6 1 7 1 8 blank beads protein A beads JR-FL - 1 3 1 4 1 5 1 6 1 7 1 8 - MGRM-C26 1 3 1 4 1 5 1 6 1 7 1 8 reciprocal serum
More informationOverview of the Joint HVTN/HPTN Research Portfolio. Theresa Gamble, PhD HPTN LOC May 15, 2018
Overview of the Joint HVTN/HPTN Research Portfolio Theresa Gamble, PhD HPTN LOC May 15, 2018 1 Joint HVTN/HPTN mab Portfolio HVTN 130/HPTN 089 HVTN 703/HPTN 081 HVTN 704/HPTN 084 AMP (VRC01) HVTN 127/HPTN
More informationBoosts Following Priming with gp120 DNA
Neutralizing Antibody Responses Induced with V3-scaffold Protein Boosts Following Priming with gp120 DNA Susan Zolla-Pazner NYU School of Medicine Problems with Whole Env Immunogens Poor induction of Abs
More informationNIAID Vaccine Research Center: A Mission to Prevent HIV Infection
NIAID Vaccine Research Center: A Mission to Prevent HIV Infection AIDS Vaccine Awareness Day 20 year anniversary May 18, 2017 Barney S. Graham, MD, PhD Deputy Director Origins of the VRC 1997 1998
More information2005 LANDES BIOSCIENCE. DO NOT DISTRIBUTE.
[Human Vaccines 1:2, 45-60; March/April 2005]; 2005 Landes Bioscience Review Role of Neutralizing Antibodies in Protective Immunity Against HIV Indresh K. Srivastava* Jeffrey B. Ulmer Susan W. Barnett
More informationVirus Panels for Assessing Vaccine-Elicited Neutralizing Antibodies
Virus Panels for Assessing Vaccine-Elicited Neutralizing Antibodies Michael Seaman, Ph.D. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Harvard Medical School J. Virol.
More informationRapid development of glycan-specific, broad, and potent anti HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque
Rapid development of glycan-specific, broad, and potent anti HIV-1 gp120 neutralizing antibodies in an R5 SIV/HIV chimeric virus infected macaque Laura M. Walker a, Devin Sok a, Yoshiaki Nishimura b, Olivia
More informationEstablishment and Targeting of the Viral Reservoir in Rhesus Monkeys
Establishment and Targeting of the Viral Reservoir in Rhesus Monkeys Dan H. Barouch, M.D., Ph.D. Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Ragon Institute of MGH, MIT,
More informationHIV and Challenges of Vaccine Development
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health HIV and Challenges of Vaccine Development Richard A. Koup, MD INTEREST
More informationA V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer
University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Virology Papers Virology, Nebraska Center for 4-2010 A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes
More informationGlycosylation of the ENV Spike of Primate Immunodeficiency Viruses and Antibody Neutralization
Current HIV Research, 2004, 2, 243-254 243 Glycosylation of the ENV Spike of Primate Immunodeficiency Viruses and Antibody Neutralization Cheryl A. Pikora *1,2 1 Department of Infectious Diseases, Children
More informationHIV-1 envelope glycoprotein trimers display open quaternary conformation when bound to. the gp41 MPER-directed broadly neutralizing antibody Z13e1
JVI Accepts, published online ahead of print on 17 April 2013 J. Virol. doi:10.1128/jvi.03284-12 Copyright 2013, American Society for Microbiology. All Rights Reserved. 1 2 HIV-1 envelope glycoprotein
More informationComputational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data
Computational Prediction of Broadly Neutralizing HIV-1 Antibody Epitopes from Neutralization Activity Data Andrew L. Ferguson 1, Emilia Falkowska 2,3, Laura M. Walker 3, Michael S. Seaman 4, Dennis R.
More informationEnvelope glycans of immunodeficiency virions are almost entirely oligomannose antigens
Supporting Information for: Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens Katie J. Doores *1,2, Camille Bonomelli *3, David J. Harvey 3, Snezana Vasiljevic 3, Raymond
More informationIsolation of a Broadly Neutralizing Antibody with Low Somatic Mutation from a Chronically Infected HIV-1 Patient
Isolation of a Broadly Neutralizing Antibody with Low Somatic Mutation from a Chronically Infected HIV-1 Patient Amanda Fabra García, Carolina Beltrán Pavez, Alberto Merino Mansilla, Cristina Xufré, Isabel
More informationLong-acting Antivirals Where Are We Headed? Are We Ready? Carl W. Dieffenbach, Ph.D. Director Division of AIDS, NIAID May 3, 2018
Long-acting Antivirals Where Are We Headed? Are We Ready? Carl W. Dieffenbach, Ph.D. Director Division of AIDS, NIAID May 3, 2018 Global HIV Statistics 2017 People living with HIV in 2016 New HIV infections
More informationPreferential induction of cross-group influenza A hemagglutinin stem specific memory B cells after H7N9 immunization in humans
INFECTIOUS DISEASE Preferential induction of cross-group influenza A hemagglutinin stem specific memory B cells after immunization in humans Sarah F. Andrews, 1 * M. Gordon Joyce, 1 Michael J. Chambers,
More informationPotent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop
JOURNAL OF VIROLOGY, Apr. 2011, p. 3128 3141 Vol. 85, No. 7 0022-538X/11/$12.00 doi:10.1128/jvi.02658-10 Copyright 2011, American Society for Microbiology. All Rights Reserved. Potent and Broad Neutralization
More informationThe Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions
JOURNAL OF VIROLOGY, Feb. 2009, p. 1649 1659 Vol. 83, No. 4 0022-538X/09/$08.00 0 doi:10.1128/jvi.02046-08 Copyright 2009, American Society for Microbiology. All Rights Reserved. The Human Immunodeficiency
More informationLow ds/dn Does Not Correlate With High Variation of Amino Acid Sequences Along the gp120 Protein Structure
Low ds/dn Does Not Correlate With High Variation of Amino Acid Sequences Along the gp120 Protein Structure Zach Goldstein & Jordan Detamore BIOL 368: Bioinformatics Laboratory Department of Biology Loyola
More informationLynn Morris. "Plan B"- bnabs for HIV prevention
"Plan B"- bnabs for HIV prevention Lynn Morris National Institute for Communicable Diseases, a division of the National Health Laboratory Service (NHLS) of South Africa, University of the Witwatersrand,
More informationLong-Acting Antibodies and Drugs as HIV Prevention Agents. David D. Ho, M.D.
Long-Acting Antibodies and Drugs as HIV Prevention Agents David D. Ho, M.D. the The HIV/AIDS pandemic rages on Key statistics from UNAIDS: 35M dead; 35M living with HIV 2.3M new infections a year or 6,300
More informationUpdate on Biomedical Prevention. Thomas C. Quinn, MD, MSc
Update on Biomedical Prevention Thomas C. Quinn, MD, MSc Associate Director of International Research National Institute of Allergy and Infectious Diseases Director, Johns Hopkins Center for Global Health
More informationDissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors
JOURNAL OF VIROLOGY, June 2007, p. 6548 6562 Vol. 81, No. 12 0022-538X/07/$08.00 0 doi:10.1128/jvi.02749-06 Copyright 2007, American Society for Microbiology. All Rights Reserved. Dissecting the Neutralizing
More informationMolecular architecture of the cleavage-dependent mannose. patch on a soluble HIV-1 envelope glycoprotein trimer
Molecular architecture of the cleavage-dependent mannose patch on a soluble HIV-1 envelope glycoprotein trimer Anna-Janina Behrens 1, David J. Harvey 1, Emilia Milne 1, Albert Cupo 2, Abhinav Kumar 1,
More informationBroadly Neutralizing Antibodies for HIV Eradication
DOI 10.1007/s11904-016-0299-7 HIV PATHOGENESIS AND TREATMENT (AL LANDAY, SECTION EDITOR) Broadly Neutralizing Antibodies for HIV Eradication Kathryn E. Stephenson 1,2 & Dan H. Barouch 1,2 # The Author(s)
More informationMutations in HIV-1 envelope that enhance entry with the macaque CD4 receptor alter
JVI Accepts, published online ahead of print on 5 November 2014 J. Virol. doi:10.1128/jvi.02680-14 Copyright 2014, American Society for Microbiology. All Rights Reserved. 1 2 Mutations in HIV-1 envelope
More informationof Nebraska - Lincoln
University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Virology Papers Virology, Nebraska Center for 2007 Characterization of Human Immunodeficiency Virus Type 1 Monomeric and
More informationA Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1
A Human Antibody to the CD4 Binding Site of gp120 Capable of Highly Potent but Sporadic Cross Clade Neutralization of Primary HIV-1 Johannes S. Gach 1,2 *., Heribert Quendler 1., Tommy Tong 3, Kristin
More informationMaturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection
Article Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection Graphical Abstract Authors Xueling Wu, Zhenhai Zhang,..., John R. Mascola, Lawrence Shapiro Correspondence
More informationA Path to an HIV Vaccine: GSID Consortium Activities. Faruk Sinangil, PhD 4th Annual CAVD Meeting Miami, FL December 1-4, 2009
A Path to an HIV Vaccine: GSID Consortium Activities Faruk Sinangil, PhD 4th Annual CAVD Meeting Miami, FL December 1-4, 2009 Project Goals Acquire and disseminate information that will contribute to the
More informationSupplementary information. Early development of broad neutralizing antibodies in HIV-1 infected infants
Supplementary information Early development of broad neutralizing antibodies in HIV-1 infected infants Leslie Goo, Vrasha Chohan, Ruth Nduati, Julie Overbaugh Supplementary Figure 1. Neutralization profile
More informationSupplementary Figure 1. ALVAC-protein vaccines and macaque immunization. (A) Maximum likelihood
Supplementary Figure 1. ALVAC-protein vaccines and macaque immunization. (A) Maximum likelihood tree illustrating CRF01_AE gp120 protein sequence relationships between 107 Envs sampled in the RV144 trial
More informationProgress in HIV Vaccine Development Magdalena Sobieszczyk, MD, MPH. Division of Infectious Diseases Columbia University Medical Center
Progress in HIV Vaccine Development Magdalena Sobieszczyk, MD, MPH Division of Infectious Diseases Columbia University Medical Center 1 Outline A short history of HIV vaccine design and development Describe
More informationMolecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1
Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1 The Harvard community has made this article openly available. Please share how this access benefits you. Your
More informationAn Exploration to Determine if Fab Molecules are Efficacious in Neutralizing Influenza H1 and H3 Subtypes. Nick Poulton June September 2012
An Exploration to Determine if Fab Molecules are Efficacious in Neutralizing Influenza H1 and H3 Subtypes Nick Poulton June 2012- September 2012 Epidemiology of Influenza Infection Causes between 250,000
More informationAIDSVaccine2010 Atlanta, Georgia Willy Bogers. NIH HIVRad Grant nr 5P01AI066287
HIV-1 envelope-cd4 receptor complexes elicit broad T- and B- cell immune responses as well as cross-reactive neutralizing antibodies in Rhesus macaques NIH HIVRad Grant nr 5P01AI066287 AIDSVaccine2010
More informationHIV-1 glycan density drives the persistence of the mannose patch within an infected. Running title: Longitudinal persistence of the HIV mannose patch
JVI Accepted Manuscript Posted Online 5 October 2016 J. Virol. doi:10.1128/jvi.01542-16 Copyright 2016 Coss et al. This is an open-access article distributed under the terms of the Creative Commons Attribution
More informationNovel Vaccine Products for Planned Phase I Immunogenicity Studies in Infants
Office of AIDS Research Novel Vaccine Products for Planned Phase I Immunogenicity Studies in Infants L. Jean Patterson, PhD Office of AIDS Research, NIH February 7, 2017 Office of AIDS Research OAR Responsibilities
More informationRecent Advances on the Use of Structural Biology for the Design of Novel Envelope Immunogens of HIV-1
University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Virology Papers Virology, Nebraska Center for 2013 Recent Advances on the Use of Structural Biology for the Design of Novel
More informationCS612 - Algorithms in Bioinformatics
Spring 2016 Protein Structure February 7, 2016 Introduction to Protein Structure A protein is a linear chain of organic molecular building blocks called amino acids. Introduction to Protein Structure Amine
More informationRecombinant Baculovirus Derived HIV-1 Virus-Like Particles Elicit Potent Neutralizing Antibody Responses
Recombinant Baculovirus Derived HIV-1 Virus-Like Particles Elicit Potent Neutralizing Antibody Responses Weimin Liu University of Alabama at Birmingham Introduction and Rationale Virus-like particles (VLPs)
More informationDifferential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and cell infection
Raska et al. AIDS Research and Therapy 2014, 11:23 RESEARCH Open Access Differential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and
More informationRapid Conformational Epitope Mapping of Anti-gp120 Antibodies with a Designed Mutant Panel Displayed on Yeast
Rapid Conformational Epitope Mapping of Anti-gp120 Antibodies with a Designed Mutant Panel Displayed on Yeast The MIT Faculty has made this article openly available. Please share how this access benefits
More informationYUMI YAMAGUCHI-KABATA AND TAKASHI GOJOBORI* Center for Information Biology, National Institute of Genetics, Mishima , Japan
JOURNAL OF VIROLOGY, May 2000, p. 4335 4350 Vol. 74, No. 9 0022-538X/00/$04.00 0 Copyright 2000, American Society for Microbiology. All Rights Reserved. Reevaluation of Amino Acid Variability of the Human
More informationBroadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers
Article Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers Emilia Falkowska, 1,2,3,7 Khoa M. Le, 1,2,3 Alejandra Ramos,
More informationX-ray and EM structures of a natively glycosylated HIV-1 envelope trimer
ISSN: 2059-7983 journals.iucr.org/d X-ray and EM structures of a natively glycosylated HIV-1 envelope trimer Harry B. Gristick, Haoqing Wang and Pamela J. Bjorkman Acta Cryst. (2017). D73, 822 828 IUCr
More informationAffinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Significance
Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains Daniela Fera a, Aaron G. Schmidt a, Barton F. Haynes b, Feng Gao b, Hua-Xin Liao b, Thomas B.
More informationModeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus Neutralization Efficiency
Article Modeling Virus- and Antibody-Specific Factors to Predict Human Immunodeficiency Virus Neutralization Efficiency Hillel Haim, 1,2 Ignacio Salas, 1 Kathleen McGee, 1 Noah Eichelberger, 2 Elizabeth
More informationResearch Online. Edith Cowan University. Constantinos K. Wibmer. Jinal N. Bhiman. Elin S. Gray Edith Cowan University,
Edith Cowan University Research Online ECU Publications 2013 2013 Viral Escape From HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition Of Multiple
More informationAaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA
Review Article imedpub Journals http://www.imedpub.com/ Journal of HIV & Retro Virus DOI: 10.21767/2471-9676.100036 Anti-HIV Passive Immunization in Animal Models Pengfei Wang * Aaron Diamond AIDS Research
More informationHIV Vaccine Conference
HIV Vaccine Conference The B cell response to HIV and HIV vaccines: From broadly neutralizing to non-neutralizing antibodies In memory of Dr. Charles Mérieux Organized by Fondation Mérieux Les Pensières
More informationEMERGING ISSUES IN THE HUMORAL IMMUNE RESPONSE TO HIV. (Summary of the recommendations from an Enterprise Working Group)
AIDS Vaccine 07, Seattle, August 20-23, 2007 EMERGING ISSUES IN THE HUMORAL IMMUNE RESPONSE TO HIV (Summary of the recommendations from an Enterprise Working Group) The Working Group Reston, Virginia,
More informationPiraporn Utachee 1, Panasda Isarangkura-na-ayuthaya 2, Kenzo Tokunaga 3, Kazuyoshi Ikuta 5, Naokazu Takeda 1,5 and Masanori Kameoka 1,4,5*
Utachee et al. Retrovirology 2014, 11:32 RESEARCH Open Access Impact of amino acid substitutions in the V2 and C2 regions of human immunodeficiency virus type 1 CRF01_AE envelope glycoprotein gp120 on
More informationAbout OMICS Group Conferences
About OMICS Group OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 27 with the sole aim of making
More informationChallenges in Designing HIV Env Immunogens for Developing a Vaccine
b514_chapter-13.qxd 12/4/2007 3:39 PM Page 327 Chapter 13 Challenges in Designing HIV Env Immunogens for Developing a Vaccine Indresh K. Srivastava* and R. Holland Cheng Summary HIV continues to be a major
More informationPhenylketonuria (PKU) Structure of Phenylalanine Hydroxylase. Biol 405 Molecular Medicine
Phenylketonuria (PKU) Structure of Phenylalanine Hydroxylase Biol 405 Molecular Medicine 1998 Crystal structure of phenylalanine hydroxylase solved. The polypeptide consists of three regions: Regulatory
More informationAntibody gene transfer for HIV immunoprophylaxis
Antibody gene transfer for HIV immunoprophylaxis Alejandro B Balazs & Anthony P West Jr Antibody gene transfer, which involves the delivery of genes that encode potent, broadly neutralizing antibodies
More informationBroadly neutralizing antibodies developed by an HIV+ elite neutralizer exact replication fitness cost to
JVI Accepts, published online ahead of print on 12 September 2012 J. Virol. doi:10.1128/jvi.01893-12 Copyright 2012, American Society for Microbiology. All Rights Reserved. 1 2 3 Revised JVI01893-12 Broadly
More informationIdentification and Characterization of CD4 T cells actively transcribing HIV RNA in Peripheral Blood
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Identification and Characterization of CD4 T cells actively transcribing
More informationIncreased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution
Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution Daniel P. Leaman, Michael B. Zwick* Department of Immunology and Microbial Science, The Scripps Research
More informationA Multivalent Clade C HIV-1 Env Trimer Cocktail Elicits a Higher Magnitude of. Neutralizing Antibodies than Any Individual Component.
JVI Accepts, published online ahead of print on 24 December 2014 J. Virol. doi:10.1128/jvi.03331-14 Copyright 2014, American Society for Microbiology. All Rights Reserved. 1 2 3 4 5 6 7 8 9 10 11 12 13
More informationCleavage-Independent HIV-1 Env Trimers Engineered as Soluble Native Spike Mimetics for Vaccine Design
Article Cleavage-Independent HIV-1 Env Trimers Engineered as Soluble Native Spike Mimetics for Vaccine Design Graphical Abstract Authors Shailendra Kumar Sharma, Natalia de Val,..., Andrew B. Ward, Richard
More informationSupporting Information
Supporting Information Horwitz et al. 73/pnas.35295 A Copies ml - C 3NC7 7 697 698 7 7 73 76-2 2 Days Gp2 residue G458D G459D T278A 7/36 N28 K D 28 459 A28T ID# 697 ID# 698 ID# 7 ID# 7 ID# 73 ID# 76 ID#
More informationCitation PLoS One, 2013, v. 8 n. 8, p. Article numbere 69789
Title HIV-1 envelope glycoprotein variable loops are indispensable for envelope structural integrity and virus entry Author(s) Yuan, T; Li, J; Zhang, M Citation PLoS One, 2013, v. 8 n. 8, p. Article numbere
More informationReceived Date : 21-Aug-2015 Revised Date : 21-Sep-2015 Accepted Date : 23-Sep-2015 Author Manuscript
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Received Date : 21-Aug-2015 Revised Date : 21-Sep-2015 Accepted Date : 23-Sep-2015 Article type : Invited Review
More informationTransient β-hairpin Formation in α-synuclein Monomer Revealed by Coarse-grained Molecular Dynamics Simulation
Transient β-hairpin Formation in α-synuclein Monomer Revealed by Coarse-grained Molecular Dynamics Simulation Hang Yu, 1, 2, a) Wei Han, 1, 3, b) Wen Ma, 1, 2 1, 2, 3, c) and Klaus Schulten 1) Beckman
More informationHuman antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses
Brief report Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses Natalie J. Thornburg, 1 David P. Nannemann, 2 David L. Blum, 1 Jessica A. Belser, 3 Terrence M. Tumpey,
More informationSupersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120
Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120 The Harvard community has made this article openly available. Please share how this access benefits you.
More informationThe Kitchen Sink. Glenda Gray AIDS vaccine at the cross roads: how to adapt to a new preven9on age? Monday 7 th October, 2013, Barcelona
The Kitchen Sink Glenda Gray AIDS vaccine at the cross roads: how to adapt to a new preven9on age? Monday 7 th October, 2013, Barcelona The only important slide of my presentation. All efficacy trial in
More informationIntra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1
Article Intra-Spike Crosslinking Overcomes Antibody Evasion by HIV-1 Graphical Abstract Authors Rachel P. Galimidi, Joshua S. Klein,..., Anthony P. WestJr., Pamela J. Bjorkman Correspondence bjorkman@caltech.edu
More informationP450 CYCLE. All P450s follow the same catalytic cycle of;
P450 CYCLE All P450s follow the same catalytic cycle of; 1. Initial substrate binding 2. First electron reduction 3. Oxygen binding 4. Second electron transfer 5 and 6. Proton transfer/dioxygen cleavage
More informationBiomedical Prevention Update Thomas C. Quinn, M.D.
Biomedical Prevention Update Thomas C. Quinn, M.D. Associate Director of International Research National Institute of Allergy and Infectious Diseases Director, Johns Hopkins Center for Global Health Global
More informationGeneration of Robust Antibody Responses to HIV-1 MPER Antigens in Mice Reconstituted with Cultured B cells
Generation of Robust Antibody Responses to HIV-1 MPER Antigens in Mice Reconstituted with Cultured B cells T. Matt Holl 1, Masayuki Kuraoka 1, Dongmei Liao 1, Laurent Verkoczy 2, M. Anthony Moody 2, Munir
More informationMolecular Biology. general transfer: occurs normally in cells. special transfer: occurs only in the laboratory in specific conditions.
Chapter 9: Proteins Molecular Biology replication general transfer: occurs normally in cells transcription special transfer: occurs only in the laboratory in specific conditions translation unknown transfer:
More informationClinical Evaluation the HIV-1 CD4 Binding Site-Specific Monoclonal Antibody VRC01. Barney S. Graham, MD, PhD August 8, 2014
Clinical Evaluation the HIV-1 CD4 Binding Site-Specific Monoclonal Antibody VRC01 Barney S. Graham, MD, PhD August 8, 2014 An Integrated Approach to HIV Vaccine Development MPER CD4bs V1V2 glycan V3 glycan
More informationSUMMARY STATEMENT ( Privileged Communication )
PROGRAM CONTACT: Eun-Chung Park 301-496-7453 epark@niaid.nih.gov Principal Investigator OLIN R. PHD SUMMARY STATEMENT ( Privileged Communication ) Applicant Organization: CORNELL UNIVERSITY ITHACA Application
More informationNovel Heterologous Prime-Boost Vaccine Strategies for HIV. Dan Barouch April 18, 2012
Novel Heterologous Prime-Boost Vaccine Strategies for HIV Dan Barouch April 18, 2012 Desired Features of a Next Generation HIV-1 Vaccine Candidate The RV1 study suggests that an HIV-1 vaccine is possible
More informationSupplementary Figure 1. Heavy chain sequences of 2G1 and 8M2 aligned with V H 1-69
Supplementary Figure 1. Heavy chain sequences of 2G1 and 8M2 aligned with V H 1-69 germline gene sequence. 2G1 and 8M2 acquired 14 and 18 mutations from the germline gene sequence, respectively. In 2G1,
More informationRole of the HIV-1 gp41 membrane proximal region in infection
JBC Papers in Press. Published on March 1, 2018 as Manuscript RA117.000537 The latest version is at http://www.jbc.org/cgi/doi/10.1074/jbc.ra117.000537 Distinct functions for the membrane proximal ectodomain
More information