11 results on '"Huy A. Tu"'
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2. Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection modelResearch in context
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Usha K. Nivarthi, Huy A. Tu, Matthew J. Delacruz, Jesica Swanstrom, Bhumi Patel, Anna P. Durbin, Stephen S. Whitehead, Kristen K. Pierce, Beth D. Kirkpatrick, Ralph S. Baric, Ngan Nguyen, Daniel E. Emerling, Aravinda M. de Silva, and Sean A. Diehl
- Subjects
Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Acute viral infections induce a rapid and transient increase in antibody-secreting plasmablasts. At convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible for long-term humoral immunity. Following an acute viral infection, the specific properties and relationships between antibodies produced by these B cell compartments are poorly understood. Methods: We utilized a controlled human challenge model of primary dengue virus serotype 2 (DENV2) infection to study acute and convalescent B-cell responses. Findings: The level of DENV2 replication was correlated with the magnitude of the plasmablast response. Functional analysis of plasmablast-derived monoclonal antibodies showed that the DENV2-specific response was dominated by cells producing DENV2 serotype-specific antibodies. DENV2-neutralizing antibodies targeted quaternary structure epitopes centered on domain III of the viral envelope protein (EDIII). Functional analysis of MBC and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotype-specific response in both compartments. The serum response mainly targeted DENV2 serotype-specific epitopes on EDIII. Interpretation: Our data suggest overall functional alignment of DENV2-specific responses from the plasmablast, through the MBC and LLPC compartments following primary DENV2 inflection. These results provide enhanced resolution of the temporal and specificity of the B cell compartment in viral infection and serve as framework for evaluation of B cell responses in challenge models. Funding: This study was supported by the Bill and Melinda Gates Foundation and the National Institutes of Health. Keywords: Dengue, Viral infection, Humoral immunity, Antibody
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- 2019
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3. Corrigendum to ‘‘Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model’’ [EBioMedicine 41 (2019) 465–478]
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Usha K. Nivarthi, Huy A. Tu, Matthew J. Delacruz, Jesica Swanstrom, Bhumi Patel, Anna P. Durbin, Stephen S. Whitehead, Kristen K. Pierce, Beth D. Kirkpatrick, Ralph S. Baric, Ngan Nguyen, Daniel E. Emerling, Aravinda M. de Silva, and Sean A. Diehl
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Medicine ,Medicine (General) ,R5-920 - Published
- 2020
- Full Text
- View/download PDF
4. DS@BioMed at ImageCLEFmedical Caption 2024: Enhanced Attention Mechanisms in Medical Caption Generation through Concept Detection Integration.
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Nhi Ngoc-Yen Nguyen, Huy Le Tu, Phuong Dieu Nguyen, Tan Nhat Do, Triet Minh Thai, and Thien B. Nguyen-Tat
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- 2024
5. Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model
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Huy A. Tu, Donna M. Rizzo, Sean A. Diehl, Nicholas Selig, Kristen K. Pierce, Stephen S. Whitehead, Roxana del Rio-Guerra, Korin Eckstrom, Anna P. Durbin, Seth Frietze, Beth D. Kirkpatrick, Dorothy M. Dickson, Julie A. Dragon, John P. Hanley, Samuel V. Scarpino, and Scott Tighe
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0301 basic medicine ,Serotype ,Myeloid ,viruses ,Science ,030231 tropical medicine ,General Physics and Astronomy ,Viremia ,Dengue virus ,Antibodies, Viral ,Serogroup ,medicine.disease_cause ,Article ,General Biochemistry, Genetics and Molecular Biology ,Virus ,Dengue ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Interferon ,Immunogenetics ,Humans ,Medicine ,Severe Dengue ,Multidisciplinary ,business.industry ,General Chemistry ,Dengue Virus ,Translational research ,medicine.disease ,Antibodies, Neutralizing ,Rash ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Viral infection ,Interferon Type I ,Immunology ,medicine.symptom ,Transcriptome ,Infection ,business ,medicine.drug - Abstract
About 20–25% of dengue virus (DENV) infections become symptomatic ranging from self-limiting fever to shock. Immune gene expression changes during progression to severe dengue have been documented in hospitalized patients; however, baseline or kinetic information is difficult to standardize in natural infection. Here we profile the host immunotranscriptome response in humans before, during, and after infection with a partially attenuated rDEN2Δ30 challenge virus (ClinicalTrials.gov NCT02021968). Inflammatory genes including type I interferon and viral restriction pathways are induced during DENV2 viremia and return to baseline after viral clearance, while others including myeloid, migratory, humoral, and growth factor immune regulation factors pathways are found at non-baseline levels post-viremia. Furthermore, pre-infection baseline gene expression is useful to predict rDEN2Δ30-induced immune responses and the development of rash. Our results suggest a distinct immunological profile for mild rDEN2Δ30 infection and offer new potential biomarkers for characterizing primary DENV infection., Dengue virus causes a range of inflammatory pathology but understanding critical phases of the infection during human infection has been challenging. Here the author’s present immunotranscriptomic changes during the acute and clearance phases of a dengue virus serotype 2 human challenge model.
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- 2021
6. Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model
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Jesica Swanstrom, Daniel Emerling, Kristen K. Pierce, Usha K. Nivarthi, Sean A. Diehl, Beth D. Kirkpatrick, Aravinda M. de Silva, Stephen S. Whitehead, Anna P. Durbin, Huy A. Tu, Ralph S. Baric, Ngan Nguyen, Bhumi Patel, and Matthew J. Delacruz
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0301 basic medicine ,biology ,medicine.drug_class ,General Medicine ,Dengue virus ,medicine.disease ,Monoclonal antibody ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Epitope ,3. Good health ,Dengue fever ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Viral envelope ,030220 oncology & carcinogenesis ,Humoral immunity ,Immunology ,biology.protein ,medicine ,Antibody ,B cell - Abstract
Background Acute viral infections induce a rapid and transient increase in antibody-secreting plasmablasts. At convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible for long-term humoral immunity. Following an acute viral infection, the specific properties and relationships between antibodies produced by these B cell compartments are poorly understood. Methods We utilized a controlled human challenge model of primary dengue virus serotype 2 (DENV2) infection to study acute and convalescent B-cell responses. Findings The level of DENV2 replication was correlated with the magnitude of the plasmablast response. Functional analysis of plasmablast-derived monoclonal antibodies showed that the DENV2-specific response was dominated by cells producing DENV2 serotype-specific antibodies. DENV2-neutralizing antibodies targeted quaternary structure epitopes centered on domain III of the viral envelope protein (EDIII). Functional analysis of MBC and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotype-specific response in both compartments. The serum response mainly targeted DENV2 serotype-specific epitopes on EDIII. Interpretation Our data suggest overall functional alignment of DENV2-specific responses from the plasmablast, through the MBC and LLPC compartments following primary DENV2 inflection. These results provide enhanced resolution of the temporal and specificity of the B cell compartment in viral infection and serve as framework for evaluation of B cell responses in challenge models. Funding This study was supported by the Bill and Melinda Gates Foundation and the National Institutes of Health.
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- 2019
7. A novel antigenic site spanning domains I and III of the Zika virus envelope glycoprotein is the target of strongly neutralizing human monoclonal antibodies
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Aravinda M. de Silva, Sean A. Diehl, Nancy R. Graham, Stephen D Graham, Huy A. Tu, Alena J. Markmann, Benjamin J. Doranz, Ariadna Grinyo, Edgar Davidson, and Benjamin D. McElvany
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medicine.drug_class ,Immunology ,B-cell responses ,Biology ,Antibodies, Viral ,Monoclonal antibody ,immune memory ,Microbiology ,Virus ,Epitope ,Zika virus ,Epitopes ,03 medical and health sciences ,Protein Domains ,Viral Envelope Proteins ,Viral envelope ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Neutralizing antibody ,Vero Cells ,030304 developmental biology ,B-Lymphocytes ,epitope ,0303 health sciences ,Zika Virus Infection ,030306 microbiology ,Antibodies, Monoclonal ,Zika Virus ,biology.organism_classification ,Antibodies, Neutralizing ,Flavivirus ,Viral Envelope ,Insect Science ,biology.protein ,Pathogenesis and Immunity ,monoclonal antibodies ,Antibody ,Protein Binding - Abstract
People infected with Zika virus develop durable neutralizing antibodies that prevent repeat infections. In the current study, we characterize a ZIKV-neutralizing human monoclonal antibody isolated from a patient after recovery. Our studies establish a novel site on the viral envelope that is targeted by human neutralizing antibodies. Our results are relevant to understanding how antibodies block infection and to guiding the design and evaluation of candidate vaccines., Zika virus (ZIKV), a mosquito-transmitted flavivirus, caused a large epidemic in Latin America between 2015 and 2017. Effective ZIKV vaccines and treatments are urgently needed to prevent future epidemics and severe disease sequelae. People infected with ZIKV develop strongly neutralizing antibodies linked to viral clearance and durable protective immunity. To understand the mechanisms of protective immunity and to support the development of ZIKV vaccines, we characterize here a strongly neutralizing antibody, B11F, isolated from a patient who recovered from ZIKV. Our results indicate that B11F targets a complex epitope on the virus that spans domains I and III of the envelope glycoprotein. While previous studies point to quaternary epitopes centered on domain II of the ZIKV E glycoprotein as targets of strongly neutralizing and protective human antibodies, we uncover a new site spanning domains I and III as a target of strongly neutralizing human antibodies. IMPORTANCE People infected with Zika virus develop durable neutralizing antibodies that prevent repeat infections. In the current study, we characterize a ZIKV-neutralizing human monoclonal antibody isolated from a patient after recovery. Our studies establish a novel site on the viral envelope that is targeted by human neutralizing antibodies. Our results are relevant to understanding how antibodies block infection and to guiding the design and evaluation of candidate vaccines.
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- 2020
8. Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003
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Nancy R. Graham, Stephen S. Whitehead, Anna P. Durbin, Usha K. Nivarthi, Jonathan E. Boyson, Huy A. Tu, Kristen K. Pierce, Matthew J. Delacruz, Philip Eisenhauer, Jason Botten, Aravinda Desilva, Beth D. Kirkpatrick, and Sean A. Diehl
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tetravalent live attenuated vaccine ,Plasma Cells ,CD4 T cells ,Viremia ,Dengue Vaccines ,Dengue virus ,Adaptive Immunity ,medicine.disease_cause ,Antibodies, Viral ,Vaccines, Attenuated ,General Biochemistry, Genetics and Molecular Biology ,Article ,Dengue ,protective immunity ,Immunity ,dengue vaccine ,medicine ,memory B cells ,Humans ,neutralizing antibodies ,Dengue vaccine ,B-Lymphocytes ,biology ,Flavivirus ,Dengue Virus ,Acquired immune system ,biology.organism_classification ,medicine.disease ,Virology ,Antibodies, Neutralizing ,humoral immune response ,Vaccination ,biology.protein ,serotype-specific antibodies ,Antibody ,TV003 - Abstract
Summary The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1–DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understand how vaccine viremia links adaptive immunity and development of protective antibody responses. TV003 viremia triggers an acute plasmablast response that, in combination with DENV-specific CD4+ T cells, correlates with serum neutralizing antibodies. TV003 vaccinees develop DENV2-reactive memory B cells, including serotype-specific and multivalent specificities in line with the composition of serum antibodies. There is no post-challenge plasmablast response in vaccinees, although stronger and earlier post-TV003 plasmablast responses associate with sterile humoral protection from DENV2 challenge. TV003 vaccine triggers plasmablasts and memory B cells, which, with support from CD4+ T cells, functionally link early vaccine viremia and the serum antibody responses., Graphical Abstract, Highlights The tetravalent live attenuated dengue vaccine TV003 stimulates plasmablasts Robust plasmablast response is associated with sterile protection from challenge DENV-specific memory B cells persist 6 months after vaccination DENV-specific CD4+ T cells correlate with neutralizing antibodies, Tu et al. show that the protective live attenuated tetravalent dengue vaccine stimulates early B and T cell responses to promote durable memory and neutralizing antibodies.
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- 2020
9. Stimulation of B Cell Immunity in Flavivirus-Naïve Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003
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Stephen S. Whitehead, Kristen K. Pierce, Anna P. Durbin, Aravinda Desilva, Jonathan E. Boyson, Beth D. Kirkpatrick, Jason Botten, Sean A. Diehl, Usha K. Nivarthi, Huy A. Tu, and Matthew J. Delacruz
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biology ,business.industry ,Viremia ,Dengue virus ,biology.organism_classification ,medicine.disease_cause ,Acquired immune system ,medicine.disease ,Vaccination ,Flavivirus ,Immunization ,Immunity ,Immunology ,Medicine ,business ,Dengue vaccine - Abstract
The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1-4), and protects against experimental DENV2 challenge in humans. Protection occurred with or without a secondary post-challenge rise in DENV2-specific neutralizing antibodies. Here we combined high resolution temporal sampling and analysis of antigen-specific responses after vaccination and challenge to determine the cellular underpinnings of the B cell response in relation to vaccine viremia and serum antibodies. TV003 vaccine-related viremia was associated with an acute plasmablast response that correlated with the development of serum neutralizing antibodies. At six-months following immunization, subjects had developed DENV2-specific memory B cells including serotype-specific and multi-valent responders. DENV2 challenge of vaccinees did not induce a post-challenge plasmablast response, though stronger and earlier post-vaccine plasmablast responses were associated with sterile humoral protection from DENV2 challenge (i.e. a lack of DENV2 antibody boosting). Our findings demonstrate that TV003 vaccine triggers a durable B cell response containing plasmablasts and memory B cells which functionally link early vaccine viremia and the serum antibody responses.
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- 2020
10. Human antibody response to Zika targets type-specific quaternary structure epitopes
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Benjamin J. Doranz, Natalie M. Bowman, Ashlie Thomas, Yaoska Reyes, Sean A. Diehl, Ciara Gimblet-Ochieng, Guei-Jiun Alice Liou, Edgar Davidson, Huy A. Tu, Sylvia Becker-Dreps, Ramesh Jadi, Benjamin D. McElvany, Matthew H. Collins, Helen M. Lazear, Stefan W. Metz, Filemon Bucardo, and Aravinda M. de Silva
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Male ,0301 basic medicine ,Endemic Diseases ,medicine.drug_class ,Cross Protection ,viruses ,Cross Reactions ,Dengue virus ,Antibodies, Viral ,Monoclonal antibody ,medicine.disease_cause ,Epitope ,Zika virus ,Dengue ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Viral envelope ,medicine ,Animals ,Humans ,Epidemics ,Protein Structure, Quaternary ,Antigens, Viral ,biology ,Zika Virus Infection ,Antibodies, Monoclonal ,Viral Vaccines ,Zika Virus ,General Medicine ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,Disease Models, Animal ,Flavivirus ,030104 developmental biology ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,biology.protein ,Epitopes, B-Lymphocyte ,Female ,Antibody ,Immunologic Memory ,Research Article - Abstract
The recent Zika virus (ZIKV) epidemic in the Americas has revealed rare but serious manifestations of infection. ZIKV has emerged in regions endemic for dengue virus (DENV), a closely related mosquito-borne flavivirus. Cross-reactive antibodies confound studies of ZIKV epidemiology and pathogenesis. The immune responses to ZIKV may be different in people, depending on their DENV immune status. Here, we focus on the human B cell and antibody response to ZIKV as a primary flavivirus infection to define the properties of neutralizing and protective antibodies generated in the absence of preexisting immunity to DENV. The plasma antibody and memory B cell response is highly ZIKV type–specific, and ZIKV-neutralizing antibodies mainly target quaternary structure epitopes on the viral envelope. To map viral epitopes targeted by protective antibodies, we isolated 2 type-specific monoclonal antibodies (mAbs) from a ZIKV case. Both mAbs were strongly neutralizing in vitro and protective in vivo. The mAbs recognize distinct epitopes centered on domains I and II of the envelope protein. We also demonstrate that the epitopes of these mAbs define antigenic regions commonly targeted by plasma antibodies in individuals from endemic and nonendemic regions who have recovered from ZIKV infections.
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- 2019
11. Corrigendum to ‘‘Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model’’ [EBioMedicine 41 (2019) 465–478]
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Daniel Emerling, Beth D. Kirkpatrick, Kristen K. Pierce, Matthew J. Delacruz, Stephen S. Whitehead, Anna P. Durbin, Ralph S. Baric, Bhumi Patel, Aravinda M. de Silva, Sean A. Diehl, Jesica Swanstrom, Ngan Nguyen, Usha K. Nivarthi, and Huy A. Tu
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Serotype ,Research paper ,Plasma Cells ,lcsh:Medicine ,Serogroup ,General Biochemistry, Genetics and Molecular Biology ,Dengue fever ,Dengue ,Epitopes ,Viral Envelope Proteins ,medicine ,Humans ,Longitudinal Studies ,Antibody ,B cell ,lcsh:R5-920 ,B-Lymphocytes ,business.industry ,lcsh:R ,General Medicine ,Dengue Virus ,medicine.disease ,Antibodies, Neutralizing ,Virology ,Humoral immunity ,medicine.anatomical_structure ,Viral infection ,Acute Disease ,Leukocytes, Mononuclear ,lcsh:Medicine (General) ,Corrigendum ,business ,Epitope Mapping - Abstract
Background Acute viral infections induce a rapid and transient increase in antibody-secreting plasmablasts. At convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible for long-term humoral immunity. Following an acute viral infection, the specific properties and relationships between antibodies produced by these B cell compartments are poorly understood. Methods We utilized a controlled human challenge model of primary dengue virus serotype 2 (DENV2) infection to study acute and convalescent B-cell responses. Findings The level of DENV2 replication was correlated with the magnitude of the plasmablast response. Functional analysis of plasmablast-derived monoclonal antibodies showed that the DENV2-specific response was dominated by cells producing DENV2 serotype-specific antibodies. DENV2-neutralizing antibodies targeted quaternary structure epitopes centered on domain III of the viral envelope protein (EDIII). Functional analysis of MBC and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotype-specific response in both compartments. The serum response mainly targeted DENV2 serotype-specific epitopes on EDIII. Interpretation Our data suggest overall functional alignment of DENV2-specific responses from the plasmablast, through the MBC and LLPC compartments following primary DENV2 inflection. These results provide enhanced resolution of the temporal and specificity of the B cell compartment in viral infection and serve as framework for evaluation of B cell responses in challenge models. Funding This study was supported by the Bill and Melinda Gates Foundation and the National Institutes of Health., Highlights • rDEN2Δ30 virus induced plasmablasts two weeks after infection of flavivirus-naïve human subjects. • Expanded plasmablast lineages produced type-specific antibodies including neutralizers to quaternary E protein epitopes • rDEN2Δ30-induced memory B cells retained functional, but not clonal type-specific overlap with the plasmablast response • DENV2-specific antibodies present during convalescence after rDEN2Δ30 infection are highly type-specific. • The rDEN2Δ30 challenge model is a framework against which to evaluate B cell responses to dengue natural infection and vaccination.
- Published
- 2020
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