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Clinical And Laboratory Features That Distinguish Dengue From Other Febrile Illnesses In Endemic Populations, James Potts, Alan Rothman Aug 2014

Clinical And Laboratory Features That Distinguish Dengue From Other Febrile Illnesses In Endemic Populations, James Potts, Alan Rothman

Alan Rothman

OBJECTIVE: Clinicians in resource-poor countries need to identify patients with dengue using readily-available data. The objective of this systematic review was to identify clinical and laboratory features that differentiate dengue fever (DF) and/or dengue haemorrhagic fever (DHF) from other febrile illnesses (OFI) in dengue-endemic populations. METHOD: Systematic review of the literature from 1990 to 30 October 2007 including English publications comparing dengue and OFI. RESULTS: Among 49 studies reviewed, 34 did not meet our criteria for inclusion. Of the 15 studies included, 10 were prospective cohort studies and five were case-control studies. Seven studies assessed all ages, four assessed children …


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 Aug 2014

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

Alan Rothman

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 …


Partial Agonist Effect Influences The Ctl Response To A Heterologous Dengue Virus Serotype, Jaroslav Zivny, Matthew Defronzo, William Jarry, Julie Jameson, John Cruz, Francis Ennis, Alan Rothman Aug 2014

Partial Agonist Effect Influences The Ctl Response To A Heterologous Dengue Virus Serotype, Jaroslav Zivny, Matthew Defronzo, William Jarry, Julie Jameson, John Cruz, Francis Ennis, Alan Rothman

Alan Rothman

Activation of dengue serotype-cross-reactive memory CTL during secondary dengue virus (DV) infection is thought to be important in the pathogenesis of dengue hemorrhagic fever. To model this effect, we studied the CTL responses to DV types 2 (D2V) and 3 (D3V) in PBMC from an individual previously infected with D3V. DV-specific CD8+ CTL from this donor recognized two HLA-B62-restricted epitopes on the NS3 protein, aa 71-79 (SVKKDLISY) and 235-243 (AMKGLPIRY). Both D3V-specific and D2V/D3V-cross-reactive CTL clones were detected for each epitope; all D2V-reactive CTL clones could lyse D2V-infected autologous cells. CTL responses to both epitopes were detected in bulk cultures …


Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis Aug 2014

Dominant Recognition By Human Cd8+ Cytotoxic T Lymphocytes Of Dengue Virus Nonstructural Proteins Ns3 And Ns1.2a, Anuja Mathew, Ichiro Kurane, Alan Rothman, Lingling Zeng, Margo Brinton, Francis Ennis

Alan Rothman

A severe complication of dengue virus infection, dengue hemorrhagic fever (DHF), is hypothesized to be immunologically mediated and virus-specific cytotoxic T lymphocytes (CTLs) may trigger DHF. It is also likely that dengue virus-specific CTLs are important for recovery from dengue virus infections. There is little available information on the human CD8+ T cell responses to dengue viruses. Memory CD8+CTL responses were analyzed to determine the diversity of the T cell response to dengue virus and to identify immunodominant proteins using PBMC from eight healthy adult volunteers who had received monovalent, live-attenuated candidate vaccines of the four dengue serotypes. All the …


Elevated Levels Of Soluble St2 Protein In Dengue Virus Infected Patients, Aniuska Becerra, Rajas Warke, Norma De Bosch, Alan Rothman, Irene Bosch Aug 2014

Elevated Levels Of Soluble St2 Protein In Dengue Virus Infected Patients, Aniuska Becerra, Rajas Warke, Norma De Bosch, Alan Rothman, Irene Bosch

Alan Rothman

Levels of the soluble form of the interleukin-1 receptor-like 1 protein (IL-1RL-1/ST2) are elevated in the serum of patients with diseases characterized by an inflammatory response. The objective of this study was to determine the concentration of soluble ST2 (sST2) in dengue infected patients during the course of the disease. Twenty-four patients with confirmed dengue infection, classified as dengue fever, and 11 patients with other febrile illness (OFI) were evaluated. Levels of sST2 in serum and laboratory variables usually altered during dengue infections were measured. Dengue infected patients had higher serum sST2 levels than OFI at the end of the …


Discordance Between Antibody And T Cell Responses In Recipients Of Trivalent Inactivated Influenza Vaccine, Mary Co, Laura Orphin, John Cruz, Pamela Pazoles, Alan Rothman, Francis Ennis, Masanori Terajima Aug 2014

Discordance Between Antibody And T Cell Responses In Recipients Of Trivalent Inactivated Influenza Vaccine, Mary Co, Laura Orphin, John Cruz, Pamela Pazoles, Alan Rothman, Francis Ennis, Masanori Terajima

Alan Rothman

Thirty adults were tested for humoral and cellular immune responses following immunization with the trivalent inactivated influenza vaccine. Modest but significant inverse correlations between the baseline and the fold changes in the number of IFNgamma-producing cells and the levels of neutralizing antibodies were observed. Specific increases in proliferative responses in the CD8 CD45RA+ population were noted after vaccination. Minimal correlations between neutralizing antibody titers and the number of IFNgamma-producing cells in terms of prevaccination levels or fold increases were observed. These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the …


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 Aug 2014

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

Alan Rothman

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.