Dennis R. Burton

Natural resistance of human immunodeficiency virus type 1 to the CD4bs antibody b12 conferred by a glycan and an arginine residue close to the CD4 binding loop (2008)

Duenas-Decamp, Maria J., Peters, Paul J., Burton, Dennis R., Clapham, Paul R.

The human monoclonal antibody b12 recognizes a conserved epitope on gp120 that overlaps the CD4 binding site. b12 has neutralizing activity against diverse human immunodeficiency virus type 1 (HIV-1)...

Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors (2008)

Peters, Paul J., Duenas-Decamp, Maria J., Sullivan, W. Matthew, Brown, Richard J. P., Ankghuambom, Chiambah, Luzuriaga, Katherine, ...

BACKGROUND: HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect...

Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors (2008)

Peters, Paul J, Duenas-Decamp, Maria J, Sullivan, W Matthew, Brown, Richard, Ankghuambom, Chiambah, Luzuriaga, Katherine, ...

Abstract Background HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to...

Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys (2007)

Wendelien B. Oswald, Thomas W. Geisbert, Kelly J. Davis, Joan B. Geisbert, Nancy J. Sullivan, Peter B. Jahrling, ...

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the...

Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120 (2006)

Binley, James M, Ngo-Abdalla, Stacie, Moore, Penny, Bobardt, Michael, Chatterji, Udayan, Gallay, Philippe, ...

Abstract During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope...

Strain-specified relative conformational stability of the scrapie prion protein (2001)

Peretz, David, Scott, Michael R., Groth, Darlene, Williamson, R. Anthony, Burton, Dennis R., Cohen, Fred E., ...

Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are...

Simian Immunodeficiency Virus (SIV) Envelope-Specific Fabs with High-Level Homologous Neutralizing Activity: Recovery (1997)

Joakim Glamann, Dennis R. Burton, Henrik J. Ditzel, Karen A. Kent, ...

An antibody phage display library was constructed from RNA extracted from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs...

The interaction of polyamines with DNA: a 23Na NMR study (1981)

Burton, Dennis R., Forsén, Sture, Reimarsson, Pétur

The interaction between a variety of polyamines, both naturally occurring and synthetic, and calf thymus DNA has been studied using 23Na NMR. The relaxation behaviour of 23Na reflects the extent of...

Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization

Wang, Hui, Griffiths, Michelle N., Burton, Dennis R., Ghazal, Peter

We have compared the kinetics of antibody responses in conventional and dendritic cell-targeted immunization by using a model antigen in mice. Targeting was achieved by linking the reporter antigen...

Cloning and expression of a novel human antibody–antigen pair associated with Felty's syndrome

Ditzel, Henrik J., Masaki, Yasufumi, Nielsen, Heidi, Farnaes, Lauge, Burton, Dennis R.

An increasing number of studies suggest the importance of antibodies in the pathogenesis of most systemic and organ-specific autoimmune diseases, although there is considerable controversy over the...

The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

Ditzel, Henrik J., Rosenkilde, Mette M., Garred, Peter, Wang, Meng, Koefoed, Klaus, Pedersen, Court, ...

The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the...

Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis

Williamson, R. Anthony, Burgoon, Mark P., Owens, Gregory P., Ghausi, Omar, Leclerc, Estelle, Firme, Louise, ...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS is typified by a highly clonally restricted antigen-driven...

A vaccine for HIV type 1: The antibody perspective

Burton, Dennis R.

Antibodies that bind well to the envelope spikes of immunodeficiency viruses such as HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) can offer protection or benefit if present at...

Human Antibody Responses to Mature and Immature Forms of Viral Envelope in Respiratory Syncytial Virus Infection: Significance for Subunit Vaccines

Sakurai, Hiroshi, Williamson, R. Anthony, Crowe, James E., Beeler, Judy A., Poignard, Pascal, Bastidas, Raiza B., ...

A number of antibodies generated during human respiratory syncytial virus (RSV) infection have been cloned by the phage library approach. Antibodies reactive with an immunodominant epitope on the F...

Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

De Logu, Alessandro, Williamson, R. Anthony, Rozenshteyn, Roman, Ramiro-Ibañez, Fernando, Simpson, Cindy D., Burton, Dennis R., ...

We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a...

Simian Immunodeficiency Virus (SIV) Envelope-Specific Fabs with High-Level Homologous Neutralizing Activity: Recovery from a Long-Term-Nonprogressor SIV-Infected Macaque

Glamann, Joakim, Burton, Dennis R., Ditzel, Henrik J., Kent, Karen A., Arnold, Caroline, ...

An antibody phage display library was constructed from RNA extracted from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs...

Neutralization of Human Immunodeficiency Virus Type 1 by Antibody to gp120 Is Determined Primarily by Occupancy of Sites on the Virion Irrespective of Epitope Specificity

Mondor, Isabelle, Naniche, Denise, Ditzel, Henrik J., Klasse, P. J., Burton, Dennis R., ...

We investigated the relative importance of binding site occupancy and epitope specificity in antibody neutralization of human immunodeficiency virus (HIV) type 1 (HIV-1). The neutralization of a...

Determinants of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Activation by Soluble CD4 and Monoclonal Antibodies

Sullivan, Nancy, Sun, Ying, Binley, James, Lee, Juliette, Barbas, Carlos F., ...

Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is enhanced by the binding of subneutralizing concentrations of soluble receptor, soluble CD4 (sCD4), or monoclonal antibodies...

Mapping the Prion Protein Using Recombinant Antibodies

Williamson, R. Anthony, Peretz, David, Pinilla, Clemencia, Ball, Hadyn, Bastidas, Raiza B., Rozenshteyn, Roman, ...

The fundamental event in prion disease is thought to be the posttranslational conversion of the cellular prion protein (PrPC) into a pathogenic isoform (PrPSc). The occurrence of PrPC on the cell...

Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells

Frankel, Sarah S., Steinman, Ralph M., Michael, Nelson L., Kim, Silvia Ratto, Bhardwaj, Nina, Pope, Melissa, ...

Prevention of the initial infection of mucosal dendritic cells (DC) and interruption of the subsequent transmission of HIV-1 from DC to T cells are likely to be important attributes of an effective...

Antibody Neutralization-Resistant Primary Isolates of Human Immunodeficiency Virus Type 1

Wang, Meng, Trkola, Alexandra, Binley, James M., Purtscher, Martin, Katinger, Hermann, ...

Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monoclonal antibodies and a small number of HIV-1+ human sera...

Ebola Virus Can Be Effectively Neutralized by Antibody Produced in Natural Human Infection

Maruyama, Toshiaki, Rodriguez, Luis L., Jahrling, Peter B., Sanchez, Anthony, Khan, Ali S., Nichol, Stuart T., ...

The activity of antibodies against filoviruses is poorly understood but has important consequences for vaccine design and passive prophylaxis. To investigate this activity, a panel of recombinant...

Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus

Crawford, John M., Earl, Patricia L., Moss, Bernard, Reimann, Keith A., Wyand, Michael S., Manson, Kelledy H., ...

Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human...

Identification and Characterization of a Peptide That Specifically Binds the Human, Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody b12

Zwick, Michael B., Bonnycastle, Lori L. C., Menendez, Alfredo, Irving, Melita B., Barbas, Carlos F., ...

Human monoclonal antibody (MAb) b12 recognizes a conformational epitope that overlaps the CD-4-binding site of the human immunodeficiency virus type 1 (HIV-1) envelope. MAb b12 neutralizes a broad...

Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41

Zwick, Michael B., Labrijn, Aran F., Wang, Meng, Spenlehauer, Catherine, Saphire, Erica Ollmann, Binley, James M., ...

The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few...

Antibody Protects Macaques against Vaginal Challenge with a Pathogenic R5 Simian/Human Immunodeficiency Virus at Serum Levels Giving Complete Neutralization In Vitro

Marx, Preston A., Hessell, Ann J., Luckay, Amara, Harouse, Janet, Cheng-Mayer, Cecilia, ...

A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as a coreceptor,...

Neutralization Synergy of Human Immunodeficiency Virus Type 1 Primary Isolates by Cocktails of Broadly Neutralizing Antibodies

Zwick, Michael B., Wang, Meng, Poignard, Pascal, Stiegler, Gabriela, Katinger, Hermann, Burton, Dennis R., ...

Several reports have described the existence of synergy between neutralizing monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 (HIV-1). Synergy between human MAbs b12, 2G12,...

Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120–CD4–CCR5 complexes

Moulard, Maxime, Phogat, Sanjay K., Shu, Yuuei, Labrijn, Aran F., Xiao, Xiaodong, Binley, James M., ...

HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor, typically CCR5. Here we provide evidence that...

Neutralizing Human Fab Fragments against Measles Virus Recovered by Phage Display

De Carvalho Nicacio, Cristina, Williamson, R. Anthony, Lundkvist, Åke, Burton, Dennis R., Björling, Ewa

Five human recombinant Fab fragments (Fabs) specific for measles virus (MV) proteins were isolated from three antibody phage display libraries generated from RNAs derived from bone marrow or splenic...

Enhancing the Proteolytic Maturation of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins

Binley, James M., Sanders, Rogier W., Master, Aditi, Cayanan, Charmagne S., Wiley, Cheryl L., Schiffner, Linnea, ...

In virus-infected cells, the envelope glycoprotein (Env) precursor, gp160, of human immunodeficiency virus type 1 is cleaved by cellular proteases into a fusion-competent gp120-gp41 heterodimer in...

Pre- and Postexposure Prophylaxis of Ebola Virus Infection in an Animal Model by Passive Transfer of a Neutralizing Human Antibody

Geisbert, Tom W., Maruyama, Toshiaki, Jahrling, Peter B., Burton, Dennis R.

A neutralizing human monoclonal antibody, KZ52, protects guinea pigs from lethal Ebola Zaire virus challenge. Administration before or up to 1 h after challenge resulted in dose-dependent protection...

The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of α1→2 Mannose Residues on the Outer Face of gp120

Scanlan, Christopher N., Pantophlet, Ralph, Wormald, Mark R., Ollmann Saphire, Erica, Stanfield, Robyn, Wilson, Ian A., ...

2G12 is a broadly neutralizing human monoclonal antibody against human immunodeficiency virus type-1 (HIV-1) that has previously been shown to bind to a carbohydrate-dependent epitope on gp120. Here,...

Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Gag- and Gag Peptide-Specific CD4+ T-Cell Clones from an HIV-1-Seronegative Donor following In Vitro Immunization

Venturini, Sara, Mosier, Donald E., Burton, Dennis R., Poignard, Pascal

Substantial evidence argues that human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cells play an important role in the control of HIV-1 replication in infected individuals. Moreover, it is...

Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies

Poignard, Pascal, Moulard, Maxime, Golez, Edwin, Vivona, Veronique, Franti, Michael, Venturini, Sara, ...

Virion capture assays, in which immobilized antibodies (Abs) capture virus particles, have been used to suggest that nonneutralizing Abs bind effectively to human immunodeficiency virus type 1...

Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120

Pantophlet, Ralph, Ollmann Saphire, Erica, Poignard, Pascal, Wilson, Ian A., Burton, Dennis R.

Alanine scanning mutagenesis was performed on monomeric gp120 of human immunodeficiency virus type 1 to systematically identify residues important for gp120 recognition by neutralizing and...

Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site

Herrera, Carolina, Spenlehauer, Catherine, Fung, Michael S., Burton, Dennis R., Beddows, Simon, Moore, John P.

We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the gp120 subunit of the envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 (HIV-1) can interfere...

Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form

Leclerc, Estelle, Peretz, David, Ball, Haydn, Sakurai, Hiroshi, Legname, Giuseppe, Serban, Ana, ...

It is hypothesized that infectious prions are generated as the cellular form of the prion protein (PrPC) undergoes pronounced conformational change under the direction of an infectious PrPSc...

Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120

Zwick, Michael B., Saphire, Erica O., Church, Sarah, Wang, Meng, Scott, Jamie K., ...

IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a...

Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design

Pantophlet, Ralph, Wilson, Ian A., Burton, Dennis R.

The ability to induce broadly neutralizing antibodies should be a key component of any forthcoming vaccine against human immunodeficiency virus type 1. One potential vaccine candidate, monomeric...

Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions

Binley, James M., Cayanan, Charmagne S., Wiley, Cheryl, Schülke, Norbert, Olson, William C., Burton, Dennis R.

We previously described a human immunodeficiency virus type 1 (HIV-1) envelope mutant that introduces a disulfide bridge between the gp120 surface proteins and gp41 transmembrane proteins (J. M....

A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12

Zwick, Michael B., Kelleher, Robert, Jensen, Richard, Labrijn, Aran F., Wang, Meng, ...

The V1/V2 and V3 loops are proximal to the CD4 binding site (CD4bs) of human immunodeficiency virus type 1 (HIV-1) gp120 and undergo conformational change upon CD4 receptor engagement by the HIV-1...

Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses

O'Connor, David H., Mothe, Bianca R., Weinfurter, Jason T., Fuenger, Sarah, Rehrauer, William M., Jing, Peicheng, ...

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques...

Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities

Johnson, Welkin E., Sanford, Hannah, Schwall, Linda, Burton, Dennis R., Robinson, James E., ...

Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary...

Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1

Labrijn, Aran F., Poignard, Pascal, Raja, Aarti, Zwick, Michael B., Delgado, Karla, Franti, Michael, ...

Anti-human immunodeficiency virus type 1 (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates....

Cellular Immunity Elicited by Human Immunodeficiency Virus Type 1/ Simian Immunodeficiency Virus DNA Vaccination Does Not Augment the Sterile Protection Afforded by Passive Infusion of Neutralizing Antibodies

Mascola, John R., Lewis, Mark G., VanCott, Thomas C., Stiegler, Gabriela, Katinger, Hermann, Seaman, Michael, ...

High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human...

The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5

Zwick, Michael B., Komori, H. Kiyomi, Stanfield, Robyn L., Church, Sarah, Wang, Meng, ...

The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to...

Motif-grafted antibodies containing the replicative interface of cellular PrP are specific for PrPSc

Moroncini, Gianluca, Kanu, Nnennaya, Solforosi, Laura, Abalos, Gil, Telling, Glenn C., Head, Mark, ...

Prion diseases are closely associated with the conversion of the cellular prion protein (PrPC) to an abnormal conformer (PrPSc) [Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. USA 95, 13363–13383]....

Identification and Characterization of a New Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody

Zhang, Mei-Yun, Xiao, Xiaodong, Sidorov, Igor A., Choudhry, Vidita, Cham, Fatim, Zhang, Peng Fei, ...

The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in...

Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

Binley, James M., Wrin, Terri, Korber, Bette, Zwick, Michael B., Wang, Meng, Chappey, Colombe, ...

Broadly neutralizing monoclonal antibodies (MAbs) are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design. A few rare MAbs have been intensively studied, but we...

A Dominant Role for CD8+-T-Lymphocyte Selection in Simian Immunodeficiency Virus Sequence Variation†

O'Connor, David H., McDermott, Adrian B., Krebs, Kendall C., Dodds, Elizabeth J., Miller, Jacqueline E., Gonzalez, Edna J., ...

CD8+ T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the...

Printed covalent glycan array for ligand profiling of diverse glycan binding proteins

Blixt, Ola, Head, Steve, Mondala, Tony, Scanlan, Christopher, Huflejt, Margaret E., Alvarez, Richard, ...

Here we describe a glycan microarray constructed by using standard robotic microarray printing technology to couple amine functionalized glycans to an amino-reactive glass slide. The array comprises...

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Antibodies 2F5 and 4E10 Require Surprisingly Few Crucial Residues in the Membrane-Proximal External Region of Glycoprotein gp41 To Neutralize HIV-1

Zwick, Michael B., Jensen, Richard, Church, Sarah, Wang, Meng, Stiegler, Gabriela, Kunert, Renate, ...

The conserved membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of two broadly neutralizing human monoclonal antibodies, 2F5 and 4E10, and is an...

Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages

Wahl-Jensen, Victoria, Kurz, Sabine K., Hazelton, Paul R., Schnittler, Hans-Joachim, Ströher, Ute, Burton, Dennis R., ...

Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation...

Robust hepatitis C virus infection in vitro

Zhong, Jin, Gastaminza, Pablo, Cheng, Guofeng, Kapadia, Sharookh, Kato, Takanobu, Burton, Dennis R., ...

The absence of a robust cell culture model of hepatitis C virus (HCV) infection has severely limited analysis of the HCV life cycle and the development of effective antivirals and vaccines. Here we...

Comparing Antigenicity and Immunogenicity of Engineered gp120

Selvarajah, Suganya, Puffer, Bridget, Pantophlet, Ralph, Law, Mansun, Doms, Robert W., Burton, Dennis R.

We have engineered monomeric gp120 in such a way as to favorably present the conserved epitope for the broadly neutralizing antibody b12 while lowering the exposure of epitopes recognized by some...

Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12

Calarese, Daniel A., Lee, Hing-Ken, Huang, Cheng-Yuan, Best, Michael D., Astronomo, Rena D., Stanfield, Robyn L., ...

Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope...

Human Recombinant Antimannan Immunoglobulin G1 Antibody Confers Resistance to Hematogenously Disseminated Candidiasis in Mice

Zhang, Mason X., Bohlman, M. Charlotte, Itatani, Carol, Burton, Dennis R., St. Jeor, Stephen C., ...

Mannan is a major cell wall component found in Candida species. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated...

Antibody vs. HIV in a clash of evolutionary titans

Burton, Dennis R., Stanfield, Robyn L., Wilson, Ian A.

HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of...

Structure-Function Analysis of the Epitope for 4E10, a Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody†

Brunel, Florence M., Zwick, Michael B., Cardoso, Rosa M. F., Nelson, Josh D., Wilson, Ian A., Burton, Dennis R., ...

The human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 4E10 binds to a linear, highly conserved epitope within the membrane-proximal external region of the HIV-1 envelope glycoprotein...

Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

Moore, Penny L., Crooks, Emma T., Porter, Lauren, Zhu, Ping, Cayanan, Charmagne S., Grise, Henry, ...

Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope...

Simian Immunodeficiency Virus Engrafted with Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Epitopes: Replication, Neutralization, and Survey of HIV-1-Positive Plasma

Yuste, Eloisa, Sanford, Hannah B., Carmody, Jill, Bixby, Jacqueline, Little, Susan, Zwick, Michael B., ...

To date, only a small number of anti-human immunodeficiency virus type 1 (HIV-1) monoclonal antibodies (MAbs) with relatively broad neutralizing activity have been isolated from infected individuals....

Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120

Binley, James M, Ngo-Abdalla, Stacie, Moore, Penny, Bobardt, Michael, Chatterji, Udayan, Gallay, Philippe, ...

During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with...

Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

Wilson, Nancy A., Reed, Jason, Napoe, Gnankang S., Piaskowski, Shari, Szymanski, Andy, Furlott, Jessica, ...

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether...

Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization

Wang, Hui, Griffiths, Michelle N., Burton, Dennis R., Ghazal, Peter

We have compared the kinetics of antibody responses in conventional and dendritic cell-targeted immunization by using a model antigen in mice. Targeting was achieved by linking the reporter antigen...

Cloning and expression of a novel human antibody–antigen pair associated with Felty's syndrome

Ditzel, Henrik J., Masaki, Yasufumi, Nielsen, Heidi, Farnaes, Lauge, Burton, Dennis R.

An increasing number of studies suggest the importance of antibodies in the pathogenesis of most systemic and organ-specific autoimmune diseases, although there is considerable controversy over the...

The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

Ditzel, Henrik J., Rosenkilde, Mette M., Garred, Peter, Wang, Meng, Koefoed, Klaus, Pedersen, Court, ...

The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the...

Anti-DNA antibodies are a major component of the intrathecal B cell response in multiple sclerosis

Williamson, R. Anthony, Burgoon, Mark P., Owens, Gregory P., Ghausi, Omar, Leclerc, Estelle, Firme, Louise, ...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of unknown cause that afflicts the central nervous system. MS is typified by a highly clonally restricted antigen-driven...

A vaccine for HIV type 1: The antibody perspective

Burton, Dennis R.

Antibodies that bind well to the envelope spikes of immunodeficiency viruses such as HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) can offer protection or benefit if present at...

Human Antibody Responses to Mature and Immature Forms of Viral Envelope in Respiratory Syncytial Virus Infection: Significance for Subunit Vaccines

Sakurai, Hiroshi, Williamson, R. Anthony, Crowe, James E., Beeler, Judy A., Poignard, Pascal, Bastidas, Raiza B., ...

A number of antibodies generated during human respiratory syncytial virus (RSV) infection have been cloned by the phage library approach. Antibodies reactive with an immunodominant epitope on the F...

Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

De Logu, Alessandro, Williamson, R. Anthony, Rozenshteyn, Roman, Ramiro-Ibañez, Fernando, Simpson, Cindy D., Burton, Dennis R., ...

We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a...

Simian Immunodeficiency Virus (SIV) Envelope-Specific Fabs with High-Level Homologous Neutralizing Activity: Recovery from a Long-Term-Nonprogressor SIV-Infected Macaque

Glamann, Joakim, Burton, Dennis R., Ditzel, Henrik J., Kent, Karen A., Arnold, Caroline, ...

An antibody phage display library was constructed from RNA extracted from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs...

Neutralization of Human Immunodeficiency Virus Type 1 by Antibody to gp120 Is Determined Primarily by Occupancy of Sites on the Virion Irrespective of Epitope Specificity

Mondor, Isabelle, Naniche, Denise, Ditzel, Henrik J., Klasse, P. J., Burton, Dennis R., ...

We investigated the relative importance of binding site occupancy and epitope specificity in antibody neutralization of human immunodeficiency virus (HIV) type 1 (HIV-1). The neutralization of a...

Determinants of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Activation by Soluble CD4 and Monoclonal Antibodies

Sullivan, Nancy, Sun, Ying, Binley, James, Lee, Juliette, Barbas, Carlos F., ...

Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is enhanced by the binding of subneutralizing concentrations of soluble receptor, soluble CD4 (sCD4), or monoclonal antibodies...

Mapping the Prion Protein Using Recombinant Antibodies

Williamson, R. Anthony, Peretz, David, Pinilla, Clemencia, Ball, Hadyn, Bastidas, Raiza B., Rozenshteyn, Roman, ...

The fundamental event in prion disease is thought to be the posttranslational conversion of the cellular prion protein (PrPC) into a pathogenic isoform (PrPSc). The occurrence of PrPC on the cell...

Neutralizing Monoclonal Antibodies Block Human Immunodeficiency Virus Type 1 Infection of Dendritic Cells and Transmission to T Cells

Frankel, Sarah S., Steinman, Ralph M., Michael, Nelson L., Kim, Silvia Ratto, Bhardwaj, Nina, Pope, Melissa, ...

Prevention of the initial infection of mucosal dendritic cells (DC) and interruption of the subsequent transmission of HIV-1 from DC to T cells are likely to be important attributes of an effective...

Antibody Neutralization-Resistant Primary Isolates of Human Immunodeficiency Virus Type 1

Wang, Meng, Trkola, Alexandra, Binley, James M., Purtscher, Martin, Katinger, Hermann, ...

Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monoclonal antibodies and a small number of HIV-1+ human sera...

Ebola Virus Can Be Effectively Neutralized by Antibody Produced in Natural Human Infection

Maruyama, Toshiaki, Rodriguez, Luis L., Jahrling, Peter B., Sanchez, Anthony, Khan, Ali S., Nichol, Stuart T., ...

The activity of antibodies against filoviruses is poorly understood but has important consequences for vaccine design and passive prophylaxis. To investigate this activity, a panel of recombinant...

Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus

Crawford, John M., Earl, Patricia L., Moss, Bernard, Reimann, Keith A., Wyand, Michael S., Manson, Kelledy H., ...

Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human...

Identification and Characterization of a Peptide That Specifically Binds the Human, Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody b12

Zwick, Michael B., Bonnycastle, Lori L. C., Menendez, Alfredo, Irving, Melita B., Barbas, Carlos F., ...

Human monoclonal antibody (MAb) b12 recognizes a conformational epitope that overlaps the CD-4-binding site of the human immunodeficiency virus type 1 (HIV-1) envelope. MAb b12 neutralizes a broad...

Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41

Zwick, Michael B., Labrijn, Aran F., Wang, Meng, Spenlehauer, Catherine, Saphire, Erica Ollmann, Binley, James M., ...

The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few...

Antibody Protects Macaques against Vaginal Challenge with a Pathogenic R5 Simian/Human Immunodeficiency Virus at Serum Levels Giving Complete Neutralization In Vitro

Marx, Preston A., Hessell, Ann J., Luckay, Amara, Harouse, Janet, Cheng-Mayer, Cecilia, ...

A major unknown in human immunodeficiency virus (HIV-1) vaccine design is the efficacy of antibodies in preventing mucosal transmission of R5 viruses. These viruses, which use CCR5 as a coreceptor,...

Neutralization Synergy of Human Immunodeficiency Virus Type 1 Primary Isolates by Cocktails of Broadly Neutralizing Antibodies

Zwick, Michael B., Wang, Meng, Poignard, Pascal, Stiegler, Gabriela, Katinger, Hermann, Burton, Dennis R., ...

Several reports have described the existence of synergy between neutralizing monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 (HIV-1). Synergy between human MAbs b12, 2G12,...

Broadly cross-reactive HIV-1-neutralizing human monoclonal Fab selected for binding to gp120–CD4–CCR5 complexes

Moulard, Maxime, Phogat, Sanjay K., Shu, Yuuei, Labrijn, Aran F., Xiao, Xiaodong, Binley, James M., ...

HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor, typically CCR5. Here we provide evidence that...

Neutralizing Human Fab Fragments against Measles Virus Recovered by Phage Display

De Carvalho Nicacio, Cristina, Williamson, R. Anthony, Lundkvist, Åke, Burton, Dennis R., Björling, Ewa

Five human recombinant Fab fragments (Fabs) specific for measles virus (MV) proteins were isolated from three antibody phage display libraries generated from RNAs derived from bone marrow or splenic...

Enhancing the Proteolytic Maturation of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins

Binley, James M., Sanders, Rogier W., Master, Aditi, Cayanan, Charmagne S., Wiley, Cheryl L., Schiffner, Linnea, ...

In virus-infected cells, the envelope glycoprotein (Env) precursor, gp160, of human immunodeficiency virus type 1 is cleaved by cellular proteases into a fusion-competent gp120-gp41 heterodimer in...

Pre- and Postexposure Prophylaxis of Ebola Virus Infection in an Animal Model by Passive Transfer of a Neutralizing Human Antibody

Geisbert, Tom W., Maruyama, Toshiaki, Jahrling, Peter B., Burton, Dennis R.

A neutralizing human monoclonal antibody, KZ52, protects guinea pigs from lethal Ebola Zaire virus challenge. Administration before or up to 1 h after challenge resulted in dose-dependent protection...

The Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2G12 Recognizes a Cluster of α1→2 Mannose Residues on the Outer Face of gp120

Scanlan, Christopher N., Pantophlet, Ralph, Wormald, Mark R., Ollmann Saphire, Erica, Stanfield, Robyn, Wilson, Ian A., ...

2G12 is a broadly neutralizing human monoclonal antibody against human immunodeficiency virus type-1 (HIV-1) that has previously been shown to bind to a carbohydrate-dependent epitope on gp120. Here,...

Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) Gag- and Gag Peptide-Specific CD4+ T-Cell Clones from an HIV-1-Seronegative Donor following In Vitro Immunization

Venturini, Sara, Mosier, Donald E., Burton, Dennis R., Poignard, Pascal

Substantial evidence argues that human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cells play an important role in the control of HIV-1 replication in infected individuals. Moreover, it is...

Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies

Poignard, Pascal, Moulard, Maxime, Golez, Edwin, Vivona, Veronique, Franti, Michael, Venturini, Sara, ...

Virion capture assays, in which immobilized antibodies (Abs) capture virus particles, have been used to suggest that nonneutralizing Abs bind effectively to human immunodeficiency virus type 1...

Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120

Pantophlet, Ralph, Ollmann Saphire, Erica, Poignard, Pascal, Wilson, Ian A., Burton, Dennis R.

Alanine scanning mutagenesis was performed on monomeric gp120 of human immunodeficiency virus type 1 to systematically identify residues important for gp120 recognition by neutralizing and...

Nonneutralizing Antibodies to the CD4-Binding Site on the gp120 Subunit of Human Immunodeficiency Virus Type 1 Do Not Interfere with the Activity of a Neutralizing Antibody against the Same Site

Herrera, Carolina, Spenlehauer, Catherine, Fung, Michael S., Burton, Dennis R., Beddows, Simon, Moore, John P.

We have investigated whether nonneutralizing monoclonal antibodies (MAbs) to the gp120 subunit of the envelope glycoprotein (Env) complex of human immunodeficiency virus type 1 (HIV-1) can interfere...

Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form

Leclerc, Estelle, Peretz, David, Ball, Haydn, Sakurai, Hiroshi, Legname, Giuseppe, Serban, Ana, ...

It is hypothesized that infectious prions are generated as the cellular form of the prion protein (PrPC) undergoes pronounced conformational change under the direction of an infectious PrPSc...

Molecular Features of the Broadly Neutralizing Immunoglobulin G1 b12 Required for Recognition of Human Immunodeficiency Virus Type 1 gp120

Zwick, Michael B., Saphire, Erica O., Church, Sarah, Wang, Meng, Scott, Jamie K., ...

IgG1 b12 is a broadly neutralizing antibody against human immunodeficiency virus type 1 (HIV-1). The epitope recognized by b12 overlaps the CD4 receptor-binding site (CD4bs) on gp120 and has been a...

Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design

Pantophlet, Ralph, Wilson, Ian A., Burton, Dennis R.

The ability to induce broadly neutralizing antibodies should be a key component of any forthcoming vaccine against human immunodeficiency virus type 1. One potential vaccine candidate, monomeric...

Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions

Binley, James M., Cayanan, Charmagne S., Wiley, Cheryl, Schülke, Norbert, Olson, William C., Burton, Dennis R.

We previously described a human immunodeficiency virus type 1 (HIV-1) envelope mutant that introduces a disulfide bridge between the gp120 surface proteins and gp41 transmembrane proteins (J. M....

A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12

Zwick, Michael B., Kelleher, Robert, Jensen, Richard, Labrijn, Aran F., Wang, Meng, ...

The V1/V2 and V3 loops are proximal to the CD4 binding site (CD4bs) of human immunodeficiency virus type 1 (HIV-1) gp120 and undergo conformational change upon CD4 receptor engagement by the HIV-1...

Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses

O'Connor, David H., Mothe, Bianca R., Weinfurter, Jason T., Fuenger, Sarah, Rehrauer, William M., Jing, Peicheng, ...

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques...

Assorted Mutations in the Envelope Gene of Simian Immunodeficiency Virus Lead to Loss of Neutralization Resistance against Antibodies Representing a Broad Spectrum of Specificities

Johnson, Welkin E., Sanford, Hannah, Schwall, Linda, Burton, Dennis R., Robinson, James E., ...

Simian immunodeficiency virus (SIV) of macaques isolate SIVmac239 is highly resistant to neutralization by polyclonal antisera or monoclonal antibodies, a property that it shares with most primary...

Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1

Labrijn, Aran F., Poignard, Pascal, Raja, Aarti, Zwick, Michael B., Delgado, Karla, Franti, Michael, ...

Anti-human immunodeficiency virus type 1 (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates....

Cellular Immunity Elicited by Human Immunodeficiency Virus Type 1/ Simian Immunodeficiency Virus DNA Vaccination Does Not Augment the Sterile Protection Afforded by Passive Infusion of Neutralizing Antibodies

Mascola, John R., Lewis, Mark G., VanCott, Thomas C., Stiegler, Gabriela, Katinger, Hermann, Seaman, Michael, ...

High levels of infused anti-human immunodeficiency virus type 1 (HIV-1) neutralizing monoclonal antibodies (MAbs) can completely protect macaque monkeys against mucosal chimeric simian-human...

The Long Third Complementarity-Determining Region of the Heavy Chain Is Important in the Activity of the Broadly Neutralizing Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5

Zwick, Michael B., Komori, H. Kiyomi, Stanfield, Robyn L., Church, Sarah, Wang, Meng, ...

The human monoclonal antibody 2F5 neutralizes primary human immunodeficiency virus type 1 (HIV-1) with rare breadth and potency. A crystal structure of a complex of 2F5 and a peptide corresponding to...

Motif-grafted antibodies containing the replicative interface of cellular PrP are specific for PrPSc

Moroncini, Gianluca, Kanu, Nnennaya, Solforosi, Laura, Abalos, Gil, Telling, Glenn C., Head, Mark, ...

Prion diseases are closely associated with the conversion of the cellular prion protein (PrPC) to an abnormal conformer (PrPSc) [Prusiner, S. B. (1998) Proc. Natl. Acad. Sci. USA 95, 13363–13383]....

Identification and Characterization of a New Cross-Reactive Human Immunodeficiency Virus Type 1-Neutralizing Human Monoclonal Antibody

Zhang, Mei-Yun, Xiao, Xiaodong, Sidorov, Igor A., Choudhry, Vidita, Cham, Fatim, Zhang, Peng Fei, ...

The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in...

Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

Binley, James M., Wrin, Terri, Korber, Bette, Zwick, Michael B., Wang, Meng, Chappey, Colombe, ...

Broadly neutralizing monoclonal antibodies (MAbs) are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design. A few rare MAbs have been intensively studied, but we...

A Dominant Role for CD8+-T-Lymphocyte Selection in Simian Immunodeficiency Virus Sequence Variation†

O'Connor, David H., McDermott, Adrian B., Krebs, Kendall C., Dodds, Elizabeth J., Miller, Jacqueline E., Gonzalez, Edna J., ...

CD8+ T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the...

Printed covalent glycan array for ligand profiling of diverse glycan binding proteins

Blixt, Ola, Head, Steve, Mondala, Tony, Scanlan, Christopher, Huflejt, Margaret E., Alvarez, Richard, ...

Here we describe a glycan microarray constructed by using standard robotic microarray printing technology to couple amine functionalized glycans to an amino-reactive glass slide. The array comprises...

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) Antibodies 2F5 and 4E10 Require Surprisingly Few Crucial Residues in the Membrane-Proximal External Region of Glycoprotein gp41 To Neutralize HIV-1

Zwick, Michael B., Jensen, Richard, Church, Sarah, Wang, Meng, Stiegler, Gabriela, Kunert, Renate, ...

The conserved membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of two broadly neutralizing human monoclonal antibodies, 2F5 and 4E10, and is an...

Role of Ebola Virus Secreted Glycoproteins and Virus-Like Particles in Activation of Human Macrophages

Wahl-Jensen, Victoria, Kurz, Sabine K., Hazelton, Paul R., Schnittler, Hans-Joachim, Ströher, Ute, Burton, Dennis R., ...

Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation...

Robust hepatitis C virus infection in vitro

Zhong, Jin, Gastaminza, Pablo, Cheng, Guofeng, Kapadia, Sharookh, Kato, Takanobu, Burton, Dennis R., ...

The absence of a robust cell culture model of hepatitis C virus (HCV) infection has severely limited analysis of the HCV life cycle and the development of effective antivirals and vaccines. Here we...

Comparing Antigenicity and Immunogenicity of Engineered gp120

Selvarajah, Suganya, Puffer, Bridget, Pantophlet, Ralph, Law, Mansun, Doms, Robert W., Burton, Dennis R.

We have engineered monomeric gp120 in such a way as to favorably present the conserved epitope for the broadly neutralizing antibody b12 while lowering the exposure of epitopes recognized by some...

Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12

Calarese, Daniel A., Lee, Hing-Ken, Huang, Cheng-Yuan, Best, Michael D., Astronomo, Rena D., Stanfield, Robyn L., ...

Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope...

Antibody vs. HIV in a clash of evolutionary titans

Burton, Dennis R., Stanfield, Robyn L., Wilson, Ian A.

HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of...

Human Recombinant Antimannan Immunoglobulin G1 Antibody Confers Resistance to Hematogenously Disseminated Candidiasis in Mice

Zhang, Mason X., Bohlman, M. Charlotte, Itatani, Carol, Burton, Dennis R., St. Jeor, Stephen C., ...

Mannan is a major cell wall component found in Candida species. Natural antimannan antibody is present in sera from most normal adults, but its role in host resistance to hematogenously disseminated...

Structure-Function Analysis of the Epitope for 4E10, a Broadly Neutralizing Human Immunodeficiency Virus Type 1 Antibody†

Brunel, Florence M., Zwick, Michael B., Cardoso, Rosa M. F., Nelson, Josh D., Wilson, Ian A., Burton, Dennis R., ...

The human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 4E10 binds to a linear, highly conserved epitope within the membrane-proximal external region of the HIV-1 envelope glycoprotein...

Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1

Moore, Penny L., Crooks, Emma T., Porter, Lauren, Zhu, Ping, Cayanan, Charmagne S., Grise, Henry, ...

Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope...

Simian Immunodeficiency Virus Engrafted with Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Epitopes: Replication, Neutralization, and Survey of HIV-1-Positive Plasma

Yuste, Eloisa, Sanford, Hannah B., Carmody, Jill, Bixby, Jacqueline, Little, Susan, Zwick, Michael B., ...

To date, only a small number of anti-human immunodeficiency virus type 1 (HIV-1) monoclonal antibodies (MAbs) with relatively broad neutralizing activity have been isolated from infected individuals....

Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

Wilson, Nancy A., Reed, Jason, Napoe, Gnankang S., Piaskowski, Shari, Szymanski, Andy, Furlott, Jessica, ...

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether...

Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120

Binley, James M, Ngo-Abdalla, Stacie, Moore, Penny, Bobardt, Michael, Chatterji, Udayan, Gallay, Philippe, ...

During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with...

Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys

Oswald, Wendelien B, Geisbert, Thomas W, Davis, Kelly J, Geisbert, Joan B, Sullivan, Nancy J, Jahrling, Peter B, ...

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the...

Molecular Analysis of the Human Autoantibody Response to α-Fodrin in Sjögren’s Syndrome Reveals Novel Apoptosis-Induced Specificity

Maruyama, Toshiaki, Saito, Ichiro, Hayashi, Yoshio, Kompfner, Elizabeth, Fox, Robert I., Burton, Dennis R., ...

Lymphocyte infiltration of salivary and lacrimal glands leading to diminished secretion and gland destruction as a result of apoptosis is thought to be pivotal in the pathogenesis of Sjögren’s...

An Affinity-Enhanced Neutralizing Antibody against the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 gp41 Recognizes an Epitope between Those of 2F5 and 4E10▿

Nelson, Josh D., Brunel, Florence M., Jensen, Richard, Crooks, Emma T., Cardoso, Rosa M. F., Wang, Meng, ...

The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 bears the epitopes of two broadly neutralizing antibodies (Abs), 2F5 and 4E10, making it a target for...

Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy▿ †

Law, Mansun, Cardoso, Rosa M. F., Wilson, Ian A., Burton, Dennis R.

The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of broadly neutralizing monoclonal antibodies (MAbs) 2F5, 4E10, and Z13. Here we engrafted...

Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors▿

Dhillon, Amandeep K., Donners, Helen, Pantophlet, Ralph, Johnson, Welkin E., Decker, Julie M., Shaw, George M., ...

Attempts to elicit broadly neutralizing antibody responses by human immunodeficiency virus type 1 (HIV-1) vaccine antigens have been met with limited success. To better understand the requirements...

A Recombinant Human Monoclonal Antibody to Human Metapneumovirus Fusion Protein That Neutralizes Virus In Vitro and Is Effective Therapeutically In Vivo▿ †

Williams, John V., Chen, Zhifeng, Cseke, Gabriella, Wright, David W., Keefer, Christopher J., Tollefson, Sharon J., ...

Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is a major cause of lower-respiratory-tract disease. hMPV is associated with more severe disease in infants and persons with...

Immune responses and HIV: a little order from the chaos

O'Connor, David H., Burton, Dennis R.

HIV is evolution gone mad and bad. The virus infects a person and rapidly diversifies to become a huge swarm of viruses, each equipped differently to resist the onslaught of diverse T cells and...

Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line–adapted HIV-1 Neutralization

Ugolini, Sophie, Mondor, Isabelle, Burton, Dennis R., Tilley, Shermaine A., Klasse, Per Johan, ...

Antibody-mediated neutralization of human immunodeficiency virus type–1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus–receptor binding, and interference...

Trafficking of prion proteins through a caveolae-mediated endosomal pathway

Peters, Peter J., Mironov, Alexander, Peretz, David, Van Donselaar, Elly, Leclerc, Estelle, Erpel, Susanne, ...

To understand the posttranslational conversion of the cellular prion protein (PrPC) to its pathologic conformation, it is important to define the intracellular trafficking pathway of PrPC within the...

Strain-specified relative conformational stability of the scrapie prion protein

Peretz, David, Scott, Michael R., Groth, Darlene, Williamson, R. Anthony, Burton, Dennis R., Cohen, Fred E., ...

Studies of prion biology and diseases have elucidated several new concepts, but none was more heretical than the proposal that the biological properties that distinguish different prion strains are...

Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN

Wang, Sheng-Kai, Liang, Pi-Hui, Astronomo, Rena D., Hsu, Tsui-Ling, Hsieh, Shie-Liang, Burton, Dennis R., ...

It is widely accepted that the heavily glycosylated glycoprotein gp120 on the surface of HIV-1 shields peptide epitopes from recognition by the immune system and may promote infection in vivo by...

A Glycoconjugate Antigen Based on the Recognition Motif of a Broadly Neutralizing Human Immunodeficiency Virus Antibody, 2G12, Is Immunogenic but Elicits Antibodies Unable To Bind to the Self Glycans of gp120▿

Astronomo, Rena D., Lee, Hing-Ken, Scanlan, Christopher N., Pantophlet, Ralph, Huang, Cheng-Yuan, Wilson, Ian A., ...

The glycan shield of human immunodeficiency virus type 1 (HIV-1) gp120 contributes to viral evasion from humoral immune responses. However, the shield is recognized by the HIV-1 broadly neutralizing...

Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

Reynolds, Matthew R., Weiler, Andrea M., Weisgrau, Kim L., Piaskowski, Shari M., Furlott, Jessica R., Weinfurter, Jason T., ...

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV)...

Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers

Hessell, Ann J., Rakasz, Eva G., Poignard, Pascal, Hangartner, Lars, Landucci, Gary, Forthal, Donald N., ...

Developing an immunogen that elicits broadly neutralizing antibodies (bNAbs) is an elusive but important goal of HIV vaccine research, especially after the recent failure of the leading T cell based...

Libraries against libraries for combinatorial selection of replicating antigen–antibody pairs

Bowley, Diana R., Jones, Teresa M., Burton, Dennis R., Lerner, Richard A.

Antibodies are among the most highly selective tight-binding ligands for proteins. Because the human genome project has deciphered the proteome, there is an opportunity to use combinatorial antibody...

The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions▿

Pantophlet, Ralph, Wang, Meng, Aguilar-Sino, Rowena O., Burton, Dennis R.

The human immunodeficiency virus type 1 (HIV-1) envelope spike is a heavily glycosylated trimeric structure in which protein surfaces conserved between different HIV-1 isolates are particularly well...

Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain▿

Wu, Lan, Zhou, Tongqing, Yang, Zhi-yong, Svehla, Krisha, O'Dell, Sijy, Louder, Mark K., ...

The broadly neutralizing antibody immunoglobulin G1 (IgG1) b12 binds to a conformationally conserved surface on the outer domain of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope...