标题
Nonneutralizing Functional Antibodies: a New “Old” Paradigm for HIV Vaccines
作者
关键词
-
出版物
Clinical and Vaccine Immunology
Volume 21, Issue 8, Pages 1023-1036
出版商
American Society for Microbiology
发表日期
2014-06-12
DOI
10.1128/cvi.00230-14
参考文献
相关参考文献
注意:仅列出部分参考文献,下载原文获取全部文献信息。- The promise of anti-ErbB3 monoclonals as new cancer therapeutics
- (2015) Luigi Aurisicchio et al. Oncotarget
- A Novel Role for Non-Neutralizing Antibodies against Nucleoprotein in Facilitating Resistance to Influenza Virus
- (2014) D. M. Carragher et al. JOURNAL OF IMMUNOLOGY
- HIV-1 Vaccine-Induced C1 and V2 Env-Specific Antibodies Synergize for Increased Antiviral Activities
- (2014) Justin Pollara et al. JOURNAL OF VIROLOGY
- Vaccine-Induced IgG Antibodies to V1V2 Regions of Multiple HIV-1 Subtypes Correlate with Decreased Risk of HIV-1 Infection
- (2014) Susan Zolla-Pazner et al. PLoS One
- Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection Distinguish RV144 and VAX003 Vaccines
- (2014) A. W. Chung et al. Science Translational Medicine
- Vaccine-Induced Env V1-V2 IgG3 Correlates with Lower HIV-1 Infection Risk and Declines Soon After Vaccination
- (2014) N. L. Yates et al. Science Translational Medicine
- Epitope target structures of Fc-mediated effector function during HIV-1 acquisition
- (2014) George K. Lewis et al. Current Opinion in HIV and AIDS
- Anti-HIV IgA isotypes
- (2013) Jennifer D. Watkins et al. AIDS
- Broadly Neutralizing Antiviral Antibodies
- (2013) Davide Corti et al. Annual Review of Immunology
- Predictive markers of safety and immunogenicity of adjuvanted vaccines
- (2013) Beatris Mastelic et al. BIOLOGICALS
- Protective Efficacy of a Global HIV-1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys
- (2013) Dan H. Barouch et al. CELL
- Complex Correlates of Protection After Vaccination
- (2013) S. A. Plotkin CLINICAL INFECTIOUS DISEASES
- Fc Receptor-Mediated Immune Responses: New Tools But Increased Complexity in HIV Prevention
- (2013) Diego Vargas-Inchaustegui et al. CURRENT HIV RESEARCH
- Protective Antiviral Antibodies that Lack Neutralizing Activity: Precedents and Evolution of Concepts
- (2013) Alan Schmaljohn CURRENT HIV RESEARCH
- HIV-1 Variable Loop 2 and its Importance in HIV-1 Infection and Vaccine Development
- (2013) Mangala Rao et al. CURRENT HIV RESEARCH
- HIV-Specific Antibody Immunity Mediated Through NK Cells and Monocytes
- (2013) Marit Kramski et al. CURRENT HIV RESEARCH
- Non-neutralizing antibodies protect from chronic LCMV infection independently of activating FcγR or complement
- (2013) Kirsten Richter et al. EUROPEAN JOURNAL OF IMMUNOLOGY
- Vaccine Induction of Antibodies against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2
- (2013) Hua-Xin Liao et al. IMMUNITY
- Neutralizing antibodies to HIV-1 induced by immunization
- (2013) Laura E. McCoy et al. JOURNAL OF EXPERIMENTAL MEDICINE
- Age-Associated Cross-reactive Antibody-Dependent Cellular Cytotoxicity Toward 2009 Pandemic Influenza A Virus Subtype H1N1
- (2013) Sinthujan Jegaskanda et al. JOURNAL OF INFECTIOUS DISEASES
- Infectious Virion Capture by HIV-1 gp120-Specific IgG from RV144 Vaccinees
- (2013) P. Liu et al. JOURNAL OF VIROLOGY
- The Canarypox Virus Vector ALVAC Induces Distinct Cytokine Responses Compared to the Vaccinia Virus-Based Vectors MVA and NYVAC in Rhesus Monkeys
- (2013) J. E. Teigler et al. JOURNAL OF VIROLOGY
- Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial
- (2013) G. H. Kijak et al. JOURNAL OF VIROLOGY
- Delayed Sequelae of Neonatal Respiratory Syncytial Virus Infection Are Dependent on Cells of the Innate Immune System
- (2013) J. A. Harker et al. JOURNAL OF VIROLOGY
- Identification of Dominant Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Antigen of Pandemic H1N1 Influenza Virus
- (2013) V. Srivastava et al. JOURNAL OF VIROLOGY
- Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques
- (2013) S. Jegaskanda et al. JOURNAL OF VIROLOGY
- Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques
- (2013) C Moog et al. Mucosal Immunology
- Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV
- (2013) Mario Roederer et al. NATURE
- Love the one you're with: the HIV, B cell and TFH cell triangle
- (2013) Shiv Pillai NATURE MEDICINE
- Inadequate T follicular cell help impairs B cell immunity during HIV infection
- (2013) Rafael A Cubas et al. NATURE MEDICINE
- Key roles of adjuvants in modern vaccines
- (2013) Steven G Reed et al. NATURE MEDICINE
- Efficacy Trial of a DNA/rAd5 HIV-1 Preventive Vaccine
- (2013) Scott M. Hammer et al. NEW ENGLAND JOURNAL OF MEDICINE
- Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes
- (2013) Geert Leroux-Roels et al. PLoS One
- Analysis of V2 Antibody Responses Induced in Vaccinees in the ALVAC/AIDSVAX HIV-1 Vaccine Efficacy Trial
- (2013) Susan Zolla-Pazner et al. PLoS One
- Affinity-Purified Respiratory Syncytial Virus Antibodies from Intravenous Immunoglobulin Exert Potent Antibody-Dependent Cellular Cytotoxicity
- (2013) Nimesh Gupta et al. PLoS One
- Serum Cytokine Profiles Associated with Specific Adjuvants Used in a DNA Prime-Protein Boost Vaccination Strategy
- (2013) Rachel Buglione-Corbett et al. PLoS One
- Comparative Efficiency of HIV-1-Infected T Cell Killing by NK Cells, Monocytes and Neutrophils
- (2013) Adjoa Smalls-Mantey et al. PLoS One
- Epitope Mapping of Conformational V2-specific Anti-HIV Human Monoclonal Antibodies Reveals an Immunodominant Site in V2
- (2013) Luzia M. Mayr et al. PLoS One
- Plasma IgG to Linear Epitopes in the V2 and V3 Regions of HIV-1 gp120 Correlate with a Reduced Risk of Infection in the RV144 Vaccine Efficacy Trial
- (2013) Raphael Gottardo et al. PLoS One
- Differential Binding of IgG and IgA to Mucus of the Female Reproductive Tract
- (2013) Kelly M. Fahrbach et al. PLoS One
- DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge
- (2013) V. Patel et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG
- (2013) G. D. Tomaras et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Obstacles to ideal anti-HIV antibody-dependent cellular cytotoxicity responses
- (2013) Leia H. Wren et al. VACCINE
- HIV/SIV DNA vaccine combined with protein in a co-immunization protocol elicits highest humoral responses to envelope in mice and macaques
- (2013) Jinyao Li et al. VACCINE
- Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines
- (2013) Wayne C. Koff et al. VACCINE
- Nanoparticle vaccines
- (2013) Liang Zhao et al. VACCINE
- Improvement of antibody responses by HIV envelope DNA and protein co-immunization
- (2013) Franco Pissani et al. VACCINE
- New paradigms for functional HIV-specific nonneutralizing antibodies
- (2013) Don Forthal et al. Current Opinion in HIV and AIDS
- HIV Transmission
- (2013) G. M. Shaw et al. Cold Spring Harbor Perspectives in Medicine
- Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity
- (2013) Brian J. Laidlaw et al. PLoS Pathogens
- The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells
- (2013) Sandeep Gupta et al. PLoS Pathogens
- Physiochemical and Biochemical Factors Influencing the Pharmacokinetics of Antibody Therapeutics
- (2012) Daniela Bumbaca et al. AAPS Journal
- The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120
- (2012) Nicos Karasavvas et al. AIDS RESEARCH AND HUMAN RETROVIRUSES
- Comprehensive Investigation of Common Antibody-Dependent Cell-Mediated Cytotoxicity Antibody Epitopes of HIV-1 CRF01_AE gp120
- (2012) Silawun Ampol et al. AIDS RESEARCH AND HUMAN RETROVIRUSES
- High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza
- (2012) Kelvin K. W. To et al. Clinical and Vaccine Immunology
- Nomenclature for Immune Correlates of Protection After Vaccination
- (2012) S. A. Plotkin et al. CLINICAL INFECTIOUS DISEASES
- Adjuvants for human vaccines
- (2012) Carl R Alving et al. CURRENT OPINION IN IMMUNOLOGY
- Non-neutralizing antibodies in prevention of HIV infection
- (2012) Harriet L. Robinson EXPERT OPINION ON BIOLOGICAL THERAPY
- CD4 T follicular helper cell dynamics during SIV infection
- (2012) Constantinos Petrovas et al. JOURNAL OF CLINICAL INVESTIGATION
- Immunity to the Conserved Influenza Nucleoprotein Reduces Susceptibility to Secondary Bacterial Infections
- (2012) L. Haynes et al. JOURNAL OF IMMUNOLOGY
- The Thai Phase III Trial (RV144) Vaccine Regimen Induces T Cell Responses That Preferentially Target Epitopes within the V2 Region of HIV-1 Envelope
- (2012) M. S. de Souza et al. JOURNAL OF IMMUNOLOGY
- Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials
- (2012) D. C. Montefiori et al. JOURNAL OF INFECTIOUS DISEASES
- Early Appearance of Neutralizing Immunoglobulin G3 Antibodies Is Associated With Chikungunya Virus Clearance and Long-term Clinical Protection
- (2012) Yiu-Wing Kam et al. JOURNAL OF INFECTIOUS DISEASES
- Immunization of Macaques With Soluble HIV Type 1 and Influenza Virus Envelope Glycoproteins Results in a Similarly Rapid Contraction of Peripheral B-Cell Responses After Boosting
- (2012) Christopher Sundling, Paola Martinez, Martina Soldemo, Mats Spångberg, Karin Lövgren Bengtsson, Linda Stertman, Mattias N. E. Forsell et al. JOURNAL OF INFECTIOUS DISEASES
- Extended Evaluation of the Virologic, Immunologic, and Clinical Course of Volunteers Who Acquired HIV-1 Infection in a Phase III Vaccine Trial of ALVAC-HIV and AIDSVAX B/E
- (2012) Supachai Rerks-Ngarm et al. JOURNAL OF INFECTIOUS DISEASES
- Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies from an HIV-1 Vaccine Efficacy Trial Target Multiple Epitopes and Preferentially Use the VH1 Gene Family
- (2012) M. Bonsignori et al. JOURNAL OF VIROLOGY
- Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion
- (2012) S. Munir Alam et al. JOURNAL OF VIROLOGY
- A Short Segment of the HIV-1 gp120 V1/V2 Region Is a Major Determinant of Resistance to V1/V2 Neutralizing Antibodies
- (2012) N. A. Doria-Rose et al. JOURNAL OF VIROLOGY
- A Nonfucosylated Variant of the anti-HIV-1 Monoclonal Antibody b12 Has Enhanced Fc RIIIa-Mediated Antiviral Activity In Vitro but Does Not Improve Protection against Mucosal SHIV Challenge in Macaques
- (2012) B. Moldt et al. JOURNAL OF VIROLOGY
- Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIVmac251Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial
- (2012) Poonam Pegu et al. JOURNAL OF VIROLOGY
- HIV-1 gp120 Vaccine Induces Affinity Maturation in both New and Persistent Antibody Clonal Lineages
- (2012) M. A. Moody et al. JOURNAL OF VIROLOGY
- Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144
- (2012) Merlin L Robb et al. LANCET INFECTIOUS DISEASES
- Human cervicovaginal mucus contains an activity that hinders HIV-1 movement
- (2012) S A Shukair et al. Mucosal Immunology
- Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2
- (2012) Morgane Rolland et al. NATURE
- Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys
- (2012) Dan H. Barouch et al. NATURE
- Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial
- (2012) Barton F. Haynes et al. NEW ENGLAND JOURNAL OF MEDICINE
- Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding
- (2012) Gerald R. Nakamura et al. PLoS One
- Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction
- (2012) J. J. Moon et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- The mechanism of action of MF59 – An innately attractive adjuvant formulation
- (2012) D.T. O’Hagan et al. VACCINE
- Non healing leg ulcer infected withStenotrophomonas maltophilia: first reported case from India
- (2012) Falguni Nag et al. International Wound Journal
- HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads
- (2012) Jennifer Mabuka et al. PLoS Pathogens
- The broadly neutralizing HIV-1 IgG 2F5 elicits gp41-specific antibody-dependent cell cytotoxicity in a FcγRI-dependent manner
- (2011) Daniela Tudor et al. AIDS
- High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses
- (2011) Justin Pollara et al. CYTOMETRY PART A
- Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems
- (2011) Nathalie Garçon et al. Expert Review of Vaccines
- HIV Vaccine efficacy trial: Glimmers of hope and the potential role of antibody-dependent cellular cytotoxicity
- (2011) Leia Wren et al. Human vaccines & immunotherapeutics
- Immunization with HIV-1 gp41 Subunit Virosomes Induces Mucosal Antibodies Protecting Nonhuman Primates against Vaginal SHIV Challenges
- (2011) Morgane Bomsel et al. IMMUNITY
- Statistical Interpretation of the RV144 HIV Vaccine Efficacy Trial in Thailand: A Case Study for Statistical Issues in Efficacy Trials
- (2011) P. B. Gilbert et al. JOURNAL OF INFECTIOUS DISEASES
- An HIV-1 gp120 Envelope Human Monoclonal Antibody That Recognizes a C1 Conformational Epitope Mediates Potent Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity and Defines a Common ADCC Epitope in Human HIV-1 Serum
- (2011) G. Ferrari et al. JOURNAL OF VIROLOGY
- A Panel of IgG1 b12 Variants with Selectively Diminished or Enhanced Affinity for Fc Receptors To Define the Role of Effector Functions in Protection against HIV
- (2011) B. Moldt et al. JOURNAL OF VIROLOGY
- Altered distribution of mucosal NK cells during HIV infection
- (2011) M Sips et al. Mucosal Immunology
- Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
- (2011) Jason S. McLellan et al. NATURE
- Germinal center B and follicular helper T cells: siblings, cousins or just good friends?
- (2011) Stephen L Nutt et al. NATURE IMMUNOLOGY
- Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
- (2011) James J. Moon et al. NATURE MATERIALS
- Moving ahead an HIV vaccine: To neutralize or not, a key HIV vaccine question
- (2011) Thomas J Hope NATURE MEDICINE
- Antibodies in oncology
- (2011) Vinochani Pillay et al. New Biotechnology
- Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody
- (2011) D. R. Burton et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure
- (2011) A. W. Chung et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing
- (2011) X. Wu et al. SCIENCE
- Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding
- (2011) J. F. Scheid et al. SCIENCE
- Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys
- (2011) N. L. Letvin et al. Science Translational Medicine
- HLA class II restriction of HIV-1 clade-specific neutralizing antibody responses in ethnic Thai recipients of the RV144 prime-boost vaccine combination of ALVAC-HIV and AIDSVAX® B/E
- (2011) Robert Paris et al. VACCINE
- IgG Subclass Profiles in Infected HIV Type 1 Controllers and Chronic Progressors and in Uninfected Recipients of Env Vaccines
- (2010) Kaustuv Banerjee et al. AIDS RESEARCH AND HUMAN RETROVIRUSES
- Correlates of Protection Induced by Vaccination
- (2010) S. A. Plotkin Clinical and Vaccine Immunology
- Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling
- (2010) Elissa K. Deenick et al. IMMUNITY
- Smallpox vaccines: targets of protective immunity
- (2010) Bernard Moss IMMUNOLOGICAL REVIEWS
- Mechanisms that determine plasma cell lifespan and the duration of humoral immunity
- (2010) Ian J. Amanna et al. IMMUNOLOGICAL REVIEWS
- Fc-Glycosylation Influences Fc Receptor Binding and Cell-Mediated Anti-HIV Activity of Monoclonal Antibody 2G12
- (2010) D. N. Forthal et al. JOURNAL OF IMMUNOLOGY
- Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection
- (2010) M. D. Parker et al. JOURNAL OF VIROLOGY
- Multiple Vaccine-Elicited Nonneutralizing Antienvelope Antibody Activities Contribute to Protective Efficacy by Reducing both Acute and Chronic Viremia following Simian/Human Immunodeficiency Virus SHIV89.6P Challenge in Rhesus Macaques
- (2010) P. Xiao et al. JOURNAL OF VIROLOGY
- Strong and persistent CD4+ T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems
- (2010) Isabel Leroux-Roels et al. VACCINE
- Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms
- (2010) Devon J. Shedlock et al. VIROLOGY
- Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient
- (2010) John S Schieffelin et al. Virology Journal
- Contribution of Nonneutralizing Vaccine-Elicited Antibody Activities to Improved Protective Efficacy in Rhesus Macaques Immunized with Tat/Env Compared with Multigenic Vaccines
- (2009) R. H. Florese et al. JOURNAL OF IMMUNOLOGY
- Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
- (2009) Supachai Rerks-Ngarm et al. NEW ENGLAND JOURNAL OF MEDICINE
- Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection
- (2009) Y. Guan et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- The integrin 4 7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1
- (2009) C. Cicala et al. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Feline leukemia virus immunity induced by whole inactivated virus vaccination
- (2009) Andrea N. Torres et al. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
- Antibody-Mediated Fcγ Receptor-Based Mechanisms of HIV Inhibition: Recent Findings and New Vaccination Strategies
- (2009) Vincent Holl et al. Viruses-Basel
- Correlation of Vaccine-Elicited Systemic and Mucosal Nonneutralizing Antibody Activities with Reduced Acute Viremia following Intrarectal Simian Immunodeficiency Virus SIVmac251 Challenge of Rhesus Macaques
- (2008) R. Hidajat et al. JOURNAL OF VIROLOGY
- HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case–cohort analysis
- (2008) M Juliana McElrath et al. LANCET
- Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial
- (2008) Susan P Buchbinder et al. LANCET
- HIV-1 envelope protein binds to and signals through integrin α4β7, the gut mucosal homing receptor for peripheral T cells
- (2008) James Arthos et al. NATURE IMMUNOLOGY
Publish scientific posters with Peeref
Peeref publishes scientific posters from all research disciplines. Our Diamond Open Access policy means free access to content and no publication fees for authors.
Learn MoreAdd your recorded webinar
Do you already have a recorded webinar? Grow your audience and get more views by easily listing your recording on Peeref.
Upload Now