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Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj
Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj
Sharone Green
The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Sharone Green
Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Development Of Antigen-Specific Memory Cd8+ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination, Heidi Smith, Thomas Monath, Pamela Pazoles, Alan Rothman, Diane Casey, Masanori Terajima, Francis Ennis, Farshad Guirakhoo, Sharone Green
Sharone Green
ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T …
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Predominance Of Hla-Restricted Cytotoxic T-Lymphocyte Responses To Serotype-Cross-Reactive Epitopes On Nonstructural Proteins Following Natural Secondary Dengue Virus Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, Henry Stephens, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Dasnayanee Chandanayingyong, Francis Ennis, Alan Rothman
Sharone Green
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA …
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Dengue Virus-Reactive Cd8+ T Cells Display Quantitative And Qualitative Differences In Their Response To Variant Epitopes Of Heterologous Viral Serotypes, Hema Bashyam, Sharone Green, Alan Rothman
Sharone Green
Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the …
Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Cytokine Gene Expression And Protein Production In Peripheral Blood Mononuclear Cells Of Children With Acute Dengue Virus Infections, Susan Gagnon, Masuko Mori, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Sharone Green
Plasma leakage in dengue hemorrhagic fever (DHF) is associated with elevated plasma levels of cytokines. To define further the contribution of immune activation to DHF and the source of cytokines, we analyzed the production of cytokines in peripheral blood mononuclear cells (PBMC) obtained from children with dengue, using RT-PCR and immunostaining. Tumor necrosis factor-alpha (TNF-alpha) and TNF-beta expression was detected in all samples by PCR and in < 50% of samples by immunostaining. Interferon-gamma (IFN-gamma) expression was detected in < 50% of samples by either method. Interleukin-2 (IL-2) and IL-4 expression was detected in a few samples by immunostaining but was not …
The Safety And Tolerability Of An Hiv-1 Dna Prime-Protein Boost Vaccine (Dp6-001) In Healthy Adult Volunteers, Jeffrey Kennedy, Mary Co, Sharone Green, Karen Longtine, Jaclyn Longtine, Melissa O'Neill, Janice Adams, Alan Rothman, Qiao Yu, Renita Johnson-Leva, Ranajit Pal, Shixia Wang, Shan Lu, Phillip Markham
The Safety And Tolerability Of An Hiv-1 Dna Prime-Protein Boost Vaccine (Dp6-001) In Healthy Adult Volunteers, Jeffrey Kennedy, Mary Co, Sharone Green, Karen Longtine, Jaclyn Longtine, Melissa O'Neill, Janice Adams, Alan Rothman, Qiao Yu, Renita Johnson-Leva, Ranajit Pal, Shixia Wang, Shan Lu, Phillip Markham
Sharone Green
This report describes the safety observations following administration of a polyvalent DNA prime-protein boost HIV-1 vaccine formulated with adjuvant QS21. Local injection site reactions were the most common (65% of subjects), and included type IV delayed-type hypersensitivity (DTH) reactions at prior DNA inoculation sites in 12 of 28 (43%) subjects following protein vaccination. Systemic reactions revealed two cases of vasculitis temporally related to inoculation with recombinant Env protein+QS21 adjuvant. Questions remain regarding the cause of the vasculitis, but the unique DTH observation may have contributed to the high level of immune responses previously reported for this vaccine.
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Sharone Green
An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNgamma ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 …