Access the full text.
Sign up today, get DeepDyve free for 14 days.
C. Anthony, Talita York, V. Bekker, David Matten, P. Selhorst, R. Ferreria, N. Garrett, S. Karim, L. Morris, N. Wood, P. Moore, C. Williamson (2017)
Cooperation between Strain-Specific and Broadly Neutralizing Responses Limited Viral Escape and Prolonged the Exposure of the Broadly Neutralizing EpitopeJournal of Virology, 91
K. Williams, M. Stumpf, Nicole Naiman, S. Ding, M. Garrett, T. Gobillot, D. Vézina, Katharine Dusenbury, Nitya Ramadoss, Ryan Basom, P. Kim, A. Finzi, J. Overbaugh (2019)
Identification of HIV gp41-specific antibodies that mediate killing of infected cellsPLoS Pathogens, 15
A. Chung, Gamze Isitman, M. Navis, M. Kramski, R. Center, S. Kent, I. Stratov (2011)
Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressureProceedings of the National Academy of Sciences, 108
K. Rantalainen, Z. Berndsen, S. Murrell, Liwei Cao, O. Omorodion, J. Torres, Mengyu Wu, J. Umotoy, Jeffrey Copps, P. Poignard, E. Landais, J. Paulson, I. Wilson, A. Ward (2018)
Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine DesignCell Reports, 23
J. Horwitz, Y. Bar-On, Ching-Lan Lu, D. Fera, Ainsley Lockhart, J. Lorenzi, Lilian Nogueira, Jovana Golijanin, J. Scheid, M. Seaman, A. Gazumyan, S. Zolla-Pazner, M. Nussenzweig (2017)
Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In VivoCell, 170
C. Watson, J. Glanville, W. Marasco (2017)
The Individual and Population Genetics of Antibody ImmunityTrends in Immunology, 38
M. Ackerman, A. Mikhailova, E. Brown, Karen Dowell, B. Walker, C. Bailey-Kellogg, T. Suscovich, G. Alter (2016)
Polyfunctional HIV-Specific Antibody Responses Are Associated with Spontaneous HIV ControlPLoS Pathogens, 12
K. Wagh, Edward Kreider, Yingying Li, H. Barbian, G. Learn, E. Giorgi, P. Hraber, Timothy Decker, Andrew Smith, M. Gondim, Lindsey Gillis, Jamie Wandzilak, G. Chuang, Reda Rawi, F. Cai, P. Pellegrino, I. Williams, J. Overbaugh, F. Gao, P. Kwong, B. Haynes, G. Shaw, P. Borrow, M. Seaman, B. Hahn, B. Korber (2018)
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization BreadthCell reports, 25
Cassandra Simonich, K. Williams, H. Verkerke, James Williams, R. Nduati, Kelly Lee, J. Overbaugh (2016)
HIV-1 Neutralizing Antibodies with Limited Hypermutation from an InfantCell, 166
K. Wiehe, T. Bradley, R. Meyerhoff, C. Hart, W. Williams, David Easterhoff, William Faison, T. Kepler, K. Saunders, S. Alam, M. Bonsignori, B. Haynes (2018)
Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody DevelopmentCell Host & Microbe, 23
D. Sheward, J. Marais, V. Bekker, B. Murrell, Kemal Eren, J. Bhiman, M. Nonyane, N. Garrett, Z. Woodman, Q. Karim, S. Karim, L. Morris, P. Moore, C. Williamson (2018)
HIV Superinfection Drives De Novo Antibody Responses and Not Neutralization BreadthCell Host & Microbe, 24
J. Richard, M. Veillette, S. Ding, Daria Zoubchenok, Nirmin Alsahafi, M. Coutu, N. Brassard, J. Park, J. Courter, B. Melillo, Amos Smith, G. Shaw, B. Hahn, J. Sodroski, D. Kaufmann, A. Finzi (2015)
Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated CytotoxicityEBioMedicine, 3
H. Liao, M. Bonsignori, S. Alam, J. McLellan, G. Tomaras, M. Moody, D. Kozink, K. Hwang, Xi Chen, C. Tsao, Pinghuang Liu, Xiaozhi Lu, R. Parks, D. Montefiori, G. Ferrari, J. Pollara, M. Rao, Kristina Peachman, S. Santra, N. Letvin, N. Karasavvas, Zhi-yong Yang, K. Dai, M. Pancera, J. Gorman, K. Wiehe, N. Nicely, S. Rerks-Ngarm, S. Nitayaphan, J. Kaewkungwal, P. Pitisuttithum, J. Tartaglia, F. Sinangil, Jerome Kim, N. Michael, T. Kepler, P. Kwong, J. Mascola, G. Nabel, A. Pinter, S. Zolla-Pazner, B. Haynes (2013)
Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2.Immunity, 38 1
M. Kramski, A. Schorcht, A. Johnston, Gregor Lichtfuss, Gregor Lichtfuss, Sinthujan Jegaskanda, R. Rose, I. Stratov, Anthony Kelleher, Martyn French, Anthony Jaworowski, Anthony Jaworowski, Stephen Kent (2012)
Role of monocytes in mediating HIV-specific antibody-dependent cellular cytotoxicity.Journal of immunological methods, 384 1-2
S. Richardson, A. Chung, H. Natarajan, B. Mabvakure, N. Mkhize, N. Garrett, S. Karim, P. Moore, M. Ackerman, G. Alter, L. Morris (2018)
HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodiesPLoS Pathogens, 14
R. Andrabi, Ching-Yao Su, C. Liang, Sachin Shivatare, Bryan Briney, J. Voss, Salar Nawazi, Chung-Yi Wu, Chi‐Huey Wong, D. Burton (2017)
Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development.Immunity, 47 5
Ian Setliff, Wyatt McDonnell, Nagarajan Raju, Robin Bombardi, Amyn Murji, C. Scheepers, Rutendo Ziki, Charissa Mynhardt, B. Shepherd, A. Mamchak, N. Garrett, S. Karim, S. Mallal, J. Crowe, L. Morris, I. Georgiev (2018)
Multi-Donor Longitudinal Antibody Repertoire Sequencing Reveals the Existence of Public Antibody Clonotypes in HIV-1 InfectionCell Host & Microbe, 23
R. Kouyos, P. Rusert, C. Kadelka, M. Huber, A. Marzel, Hanna Ebner, M. Schanz, T. Liechti, N. Friedrich, D. Braun, A. Scherrer, J. Weber, T. Uhr, Nicolas Baumann, Christine Leemann, H. Kuster, J. Chave, M. Cavassini, E. Bernasconi, M. Hoffmann, A. Calmy, M. Battegay, A. Rauch, S. Yerly, V. Aubert, T. Klimkait, J. Böni, K. Metzner, H. Günthard, A. Trkola, The Study (2018)
Tracing HIV-1 strains that imprint broadly neutralizing antibody responsesNature, 561
M. Muenchhoff, E. Adland, Owen Karimanzira, C. Crowther, M. Pace, Anna Csala, E. Leitman, Angeline Moonsamy, C. McGregor, J. Hurst, A. Groll, M. Mori, S. Sinmyee, C. Thobakgale, G. Tudor-Williams, A. Prendergast, H. Kløverpris, J. Roider, A. Leslie, D. Shingadia, Thea Brits, Samantha Daniels, J. Frater, C. Willberg, B. Walker, T. Ndung’u, Pieter Jooste, P. Moore, L. Morris, P. Goulder (2016)
Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infectionScience Translational Medicine, 8
Saheli Sadanand, Jishnu Das, A. Chung, M. Schoen, Sophie Lane, T. Suscovich, H. Streeck, Davey Smith, S. Little, D. Lauffenburger, D. Richman, G. Alter (2017)
Temporal variation in HIV-specific IgG subclass antibodies during acute infection differentiates spontaneous controllers from chronic progressorsAIDS, 32
Sven Kratochvil, P. McKay, A. Chung, S. Kent, J. Gilmour, R. Shattock (2017)
Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 VaccinationFrontiers in Immunology, 8
Liao (2013)
453Immunity, 5
M. Ruiz, J. Salido, L. Abusamra, Y. Ghiglione, Cintia Cevallos, G. Damilano, A. Rodríguez, C. Trifone, N. Laufer, L. Giavedoni, O. Sued, H. Salomón, M. Gherardi, G. Turk (2017)
Evaluation of Different Parameters of Humoral and Cellular Immune Responses in HIV Serodiscordant Heterosexual Couples: Humoral Response Potentially Implicated in Modulating Transmission RatesEBioMedicine, 26
M. Veillette, A. Désormeaux, H. Medjahed, Nour-Elhouda Gharsallah, M. Coutu, J. Baalwa, Y. Guan, G. Lewis, G. Ferrari, B. Hahn, B. Haynes, James Robinson, D. Kaufmann, M. Bonsignori, J. Sodroski, A. Finzi (2013)
Interaction with Cellular CD4 Exposes HIV-1 Envelope Epitopes Targeted by Antibody-Dependent Cell-Mediated CytotoxicityJournal of Virology, 88
T. Bradley, D. Peppa, I. Pedroza-Pacheco, Dapeng Li, D. Cain, Ricardo Henao, V. Venkat, B. Hora, Yue Chen, N. Vandergrift, R. Overman, R. Edwards, C. Woods, G. Tomaras, G. Ferrari, G. Ginsburg, M. Connors, M. Cohen, M. Moody, P. Borrow, B. Haynes (2018)
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody ResponsesCell, 175
R. Powell, A. Fox, V. Itri, S. Zolla-Pazner (2018)
Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis ProfileJournal of Innate Immunity, 11
P. Rusert, R. Kouyos, C. Kadelka, Hanna Ebner, M. Schanz, M. Huber, D. Braun, N. Hozé, A. Scherrer, Carsten Magnus, J. Weber, T. Uhr, V. Cippà, C. Thorball, H. Kuster, M. Cavassini, E. Bernasconi, M. Hoffmann, A. Calmy, M. Battegay, A. Rauch, S. Yerly, V. Aubert, T. Klimkait, J. Böni, J. Fellay, R. Regoes, H. Günthard, A. Trkola, Heiner F, H. Bucher, A. Ciuffi, G. Dollenmaier, M. Egger, L. Elzi, J. Fehr, H. Furrer, C. Fux, D. Haerry, B. Hasse, H. Hirsch, I. Hösli, C. Kahlert, L. Kaiser, O. Keiser, H. Kovari, B. Ledergerber, G. Martinetti, B. Tejada, C. Marzolini, K. Metzner, N. Müller, D. Nicca, G. Pantaleo, P. Paioni, C. Rudin, P. Schmid, R. Speck, M. Stöckle, P. Tarr, P. Vernazza, G. Wandeler, R. Weber (2016)
Determinants of HIV-1 broadly neutralizing antibody inductionNature Medicine, 22
Maxence Duchemin, Marwa Khamassi, Lin Xu, D. Tudor, M. Bomsel (2018)
IgA Targeting Human Immunodeficiency Virus-1 Envelope gp41 Triggers Antibody-Dependent Cellular Cytotoxicity Cross-Clade and Cooperates with gp41-Specific IgG to Increase Cell LysisFrontiers in Immunology, 9
O. Scharf, H. Golding, L. King, N. Eller, D. Frazier, B. Golding, D. Scott (2001)
Immunoglobulin G3 from Polyclonal Human Immunodeficiency Virus (HIV) Immune Globulin Is More Potent than Other Subclasses in Neutralizing HIV Type 1Journal of Virology, 75
Abigail Smith, Samantha Burton, W. Kilembe, S. Lakhi, E. Karita, M. Price, S. Allen, C. Derdeyn (2019)
VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120Frontiers in Immunology, 9
M. Worley, Kuang Fei, Adam Lopez-Denman, A. Kelleher, S. Kent, A. Chung (2018)
Neutrophils mediate HIV-specific antibody-dependent phagocytosis and ADCC.Journal of immunological methods, 457
Leslie Goo, Vrasha Chohan, R. Nduati, J. Overbaugh (2014)
Early development of broad neutralizing antibodies in HIV-1 infected infantsNature medicine, 20
T. Zhou, A. Zheng, U. Baxa, G. Chuang, I. Georgiev, Rui Kong, S. O'dell, S. Shahzad-ul-Hussan, Chen-Hsiang Shen, Y. Tsybovsky, R. Bailer, S. Gift, M. Louder, K. Mckee, Reda Rawi, Catherine Stevenson, G. Stewart-Jones, J. Taft, Eric Waltari, Yongping Yang, Baoshan Zhang, Sachin Shivatare, Vidya Shivatare, C. Lee, Chung-Yi Wu, J. Mullikin, C. Bewley, D. Burton, V. Polonis, L. Shapiro, Chi‐Huey Wong, J. Mascola, P. Kwong, Xueling Wu (2018)
A Neutralizing Antibody Recognizing Primarily N‐Linked Glycan Targets the Silent Face of the HIV EnvelopeImmunity, 48
M. Veillette, M. Coutu, J. Richard, Laurie-Anne Batraville, O. Dagher, N. Bernard, C. Tremblay, D. Kaufmann, M. Roger, A. Finzi (2014)
The HIV-1 gp120 CD4-Bound Conformation Is Preferentially Targeted by Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies in Sera from HIV-1-Infected IndividualsJournal of Virology, 89
L. Kardava, H. Sohn, Christine Youn, J. Austin, Wen Wang, C. Buckner, J. Justement, Valerie Melson, Gwynne Roth, Marissa Hand, Kathleen Gittens, Richard Kwan, M. Sneller, Yuxing Li, T. Chun, P. Sun, S. Pierce, S. Moir (2018)
IgG3 regulates tissue-like memory B cells in HIV-infected individualsNature Immunology, 19
V. Oxelius, J. Pandey (2013)
Human immunoglobulin constant heavy G chain (IGHG) (Fcγ) (GM) genes, defining innate variants of IgG molecules and B cells, have impact on disease and therapy.Clinical immunology, 149 3
A. Chung, Jenniffer Mabuka, Bongiwe Ndlovu, A. Licht, H. Robinson, Yathisha Ramlakhan, M. Ghebremichael, T. Reddy, P. Goulder, B. Walker, T. Ndung’u, G. Alter (2018)
Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activityAIDS, 32
K. Williams, Bingjie Wang, Dana Arenz, James Williams, A. Dingens, V. Cortez, Cassandra Simonich, Stephanie Rainwater, Dara Lehman, Kelly Lee, J. Overbaugh (2018)
Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal RepertoireCell reports, 23
L. Reh, Carsten Magnus, C. Kadelka, D. Kühnert, T. Uhr, J. Weber, L. Morris, P. Moore, A. Trkola (2018)
Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineagePLoS Pathogens, 14
E. Landais, P. Moore (2018)
Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizersRetrovirology, 15
G. Alter, Karen Dowell, E. Brown, T. Suscovich, A. Mikhailova, Alison Mahan, B. Walker, F. Nimmerjahn, C. Bailey-Kellogg, M. Ackerman (2018)
High‐resolution definition of humoral immune response correlates of effective immunity against HIVMolecular Systems Biology, 14
C. Kadelka, T. Liechti, Hanna Ebner, M. Schanz, P. Rusert, N. Friedrich, Emanuel Stiegeler, D. Braun, M. Huber, A. Scherrer, J. Weber, T. Uhr, H. Kuster, B. Misselwitz, M. Cavassini, E. Bernasconi, M. Hoffmann, A. Calmy, M. Battegay, A. Rauch, S. Yerly, V. Aubert, T. Klimkait, J. Böni, R. Kouyos, H. Günthard, A. Trkola (2018)
Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activityThe Journal of Experimental Medicine, 215
J. Roider, T. Maehara, Abigail Ngoepe, D. Ramsuran, M. Muenchhoff, E. Adland, T. Aicher, S. Kazer, Pieter Jooste, F. Karim, Warren Kuhn, A. Shalek, T. Ndung’u, L. Morris, P. Moore, S. Pillai, H. Kløverpris, P. Goulder, A. Leslie (2018)
High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not AdultsFrontiers in Immunology, 9
R. Henderson, Brian Watts, Hieu Ergin, Kara Anasti, R. Parks, S. Xia, Ashley Trama, H. Liao, H. Liao, K. Saunders, M. Bonsignori, K. Wiehe, B. Haynes, S. Alam (2019)
Selection of immunoglobulin elbow region mutations impacts interdomain conformational flexibility in HIV-1 broadly neutralizing antibodiesNature Communications, 10
S. Richardson, C. Crowther, N. Mkhize, L. Morris (2018)
Measuring the ability of HIV-specific antibodies to mediate trogocytosis.Journal of immunological methods, 463
S. Rerks-Ngarm, P. Pitisuttithum, S. Nitayaphan, J. Kaewkungwal, J. Chiu, R. Paris, Nakorn Premsri, C. Namwat, M. Souza, Elizabeth Adams, M. Benenson, S. Gurunathan, Jim Tartaglia, J. McNeil, Donald Francis, D. Stablein, D. Birx, S. Chunsuttiwat, C. Khamboonruang, P. Thongcharoen, M. Robb, Nelson Michael, P. Kunasol, Jerome Kim (2009)
Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.The New England journal of medicine, 361 23
H. Tam, M. Melo, Myungsun Kang, Jeisa Pelet, V. Ruda, M. Foley, Joyce Hu, Sudha Kumari, Jordan Crampton, Alexis Baldeon, R. Sanders, John Moore, S. Crotty, R. Langer, Daniel Anderson, A. Chakraborty, D. Irvine (2016)
Sustained antigen availability during germinal center initiation enhances antibody responses to vaccinationProceedings of the National Academy of Sciences, 113
L. Molinos-Albert, B. Clotet, J. Blanco, J. Carrillo (2017)
Immunologic Insights on the Membrane Proximal External Region: A Major Human Immunodeficiency Virus Type-1 Vaccine TargetFrontiers in Immunology, 8
Evan Cale, J. Gorman, N. Radakovich, E. Crooks, K. Osawa, T. Tong, Jiaqi Li, Raju Nagarajan, G. Ozorowski, D. Ambrozak, M. Asokan, R. Bailer, Anthony Bennici, Xuejun Chen, N. Doria-Rose, A. Druz, Yu Feng, Gordon Joyce, M. Louder, S. O'dell, C. Oliver, M. Pancera, M. Connors, T. Hope, T. Kepler, R. Wyatt, A. Ward, I. Georgiev, P. Kwong, J. Mascola, J. Binley (2017)
Virus‐like Particles Identify an HIV V1V2 Apex‐Binding Neutralizing Antibody that Lacks a Protruding LoopImmunity, 46
J. Pollara, C. Orlandi, Charles Beck, R. Edwards, Y. Hu, Shuying Liu, Shixia Wang, R. Koup, T. Denny, Shan Lu, G. Tomaras, A. Devico, G. Lewis, G. Ferrari (2018)
Application of area scaling analysis to identify natural killer cell and monocyte involvement in the GranToxiLux antibody dependent cell‐mediated cytotoxicity assayCytometry, 93
C. Eeden, Constantinos Wibmer, C. Scheepers, S. Richardson, M. Nonyane, B. Lambson, N. Mkhize, B. Vijayakumar, Zizhang Sheng, S. Stanfield-Oakley, J. Bhiman, V. Bekker, T. Hermanus, B. Mabvakure, A. Ismail, M. Moody, K. Wiehe, N. Garrett, S. Karim, H. Dirr, M. Fernandes, Yasien Sayed, L. Shapiro, G. Ferrari, B. Haynes, P. Moore, L. Morris (2018)
V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC ActivityCell reports, 25
V. Cortez, K. Odem-Davis, R. Mcclelland, W. Jaoko, J. Overbaugh, A. Trkola (2012)
HIV-1 Superinfection in Women Broadens and Strengthens the Neutralizing Antibody ResponsePLoS Pathogens, 8
M. Ackerman, Jishnu Das, Srivamshi Pittala, Thomas Broge, C. Linde, T. Suscovich, E. Brown, T. Bradley, H. Natarajan, Shu Lin, Jessica Sassic, Sean O'Keefe, Nickita Mehta, D. Goodman, M. Sips, J. Weiner, G. Tomaras, B. Haynes, D. Lauffenburger, C. Bailey-Kellogg, M. Roederer, G. Alter (2018)
Route of immunization defines multiple mechanisms of vaccine-mediated protection against SIVNature Medicine, 24
D. Tudor, Huifeng Yu, Julien Maupetit, A. Drillet, Tahar Bouceba, I. Schwartz-Cornil, L. Lopalco, P. Tufféry, M. Bomsel (2012)
Isotype modulates epitope specificity, affinity, and antiviral activities of anti–HIV-1 human broadly neutralizing 2F5 antibodyProceedings of the National Academy of Sciences, 109
Purpose of review Although the goal of preventive HIV vaccine design is primarily the induction of broadly neutralizing antibodies (bNAbs), recent evidence suggests that a protective response will also benefit from Fc effector functions. Here, we provide an update on the antibody response to HIV infection, including both Fab and Fc-mediated antibody responses. We also highlight recent studies showing the interplay between these functions, focusing primarily on studies published in the last year. Recent findings Identification and characterization of bNAb donors continues to provide insights into viral factors that are potentially translatable to vaccine design. Improved and more diverse measures of Fc effector function, and modulators thereof, are enabling a deeper understanding of their role in infection. New data providing mechanistic links between the innate and adaptive humoral immune responses are creating exciting opportunities for vaccine strategies, with the aim of eliciting a polyfunctional protective response. Summary New insights into the overall humoral response to HIV infection are defining diverse and synergistic mechanisms required for antibody protection from HIV through vaccination. aCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service bFaculty of Health Sciences, University of the Witwatersrand, Johannesburg cCentre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa Correspondence to Penny L. Moore, Centre for HIV and STIs, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa. Tel: +27 11 386 6331; fax: +27 11 386 6333; e-mail: pennym@nicd.ac.za
Current Opinion in HIV and Aids – Wolters Kluwer Health
Published: Jul 1, 2019
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.