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Article ; Online: Dengue virus vaccine development.

Yauch, Lauren E / Shresta, Sujan

2014 Volume 88, Page(s) 315–372

Abstract: Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to ... ...

Abstract	Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.
MeSH term(s)	Dengue/epidemiology ; Dengue/immunology ; Dengue/prevention & control ; Dengue Vaccines/immunology ; Dengue Vaccines/isolation & purification ; Dengue Virus/immunology ; Drug Discovery/trends ; Humans ; Vaccines, DNA/immunology ; Vaccines, DNA/isolation & purification ; Vaccines, Inactivated/immunology ; Vaccines, Inactivated/isolation & purification ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/isolation & purification
Chemical Substances	Dengue Vaccines ; Vaccines, DNA ; Vaccines, Inactivated ; Vaccines, Synthetic
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	195-8
ISSN	1557-8399 ; 0065-3527
ISSN (online)	1557-8399
ISSN	0065-3527
DOI	10.1016/B978-0-12-800098-4.00007-6
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Article ; Online: ISPAD roving reporters 2020.

Marks, Brynn E / Harnois-Leblanc, Soren / Ng, Sze May / Perez-Garcia, E Melissa / Ahmad, Peerzada Ovais / Adhami, Sara / Mandilou, Steve Vassili Missambou / Yauch, Lauren McClure / Ehtisham, Sarah

Pediatric diabetes

2021 Volume 22, Issue 5, Page(s) 834–838

MeSH term(s)	Adolescent ; Blood Glucose Self-Monitoring/methods ; Blood Glucose Self-Monitoring/trends ; COVID-19/blood ; COVID-19/complications ; COVID-19/epidemiology ; COVID-19/therapy ; Child ; Child, Preschool ; Congresses as Topic/history ; Congresses as Topic/trends ; Cross-Cultural Comparison ; Cultural Diversity ; Developing Countries ; Diabetes Complications/blood ; Diabetes Complications/epidemiology ; Diabetes Complications/psychology ; Diabetes Complications/therapy ; Diabetes Mellitus/blood ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/psychology ; Diabetes Mellitus/therapy ; Diet ; Dyslipidemias/complications ; Dyslipidemias/epidemiology ; Dyslipidemias/therapy ; Endocrinology/history ; Endocrinology/methods ; Endocrinology/organization & administration ; Endocrinology/trends ; Female ; History, 21st Century ; Humans ; Male ; Obesity/complications ; Obesity/epidemiology ; Obesity/therapy ; Societies, Medical/history ; Societies, Medical/organization & administration ; Societies, Medical/standards ; Societies, Medical/trends ; Young Adult
Language	English
Publishing date	2021-06-09
Publishing country	Denmark
Document type	Congress ; Historical Article
ZDB-ID	1502504-4
ISSN	1399-5448 ; 1745-1426 ; 1399-543X
ISSN (online)	1399-5448
ISSN	1745-1426 ; 1399-543X
DOI	10.1111/pedi.13233
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Article ; Online: Mouse models of dengue virus infection and disease.

Yauch, Lauren E / Shresta, Sujan

Antiviral research

2008 Volume 80, Issue 2, Page(s) 87–93

Abstract: Dengue virus (DENV) causes the most significant mosquito-borne viral disease in the world in terms of illness, death, and economic cost, due to the lack of an approved vaccine or antiviral. Infections with one of the four serotypes of DENV (DENV1-4) can ... ...

Abstract	Dengue virus (DENV) causes the most significant mosquito-borne viral disease in the world in terms of illness, death, and economic cost, due to the lack of an approved vaccine or antiviral. Infections with one of the four serotypes of DENV (DENV1-4) can result in diseases ranging from an acute, self-limiting febrile illness (dengue fever, DF) to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), yet exactly how viral and host factors contribute to the severe disease is unknown. Clinical observations have provided information on DENV pathogenesis, but the lack of an adequate animal model has hindered research on this important human pathogen. A mouse model is ideal for investigating host-pathogen interactions due to the immunological tools available, however, wild-type mice are resistant to DENV-induced disease. Therefore, the mouse models for DENV infection developed to date include infection of severely immunocompromised mice, non-physiologic routes of infection, and mouse-human chimeras, which all have their limitations. An inbred mouse model in which mice develop signs of human DENV-induced disease is needed to investigate the contribution of various immune components to protection and pathogenesis of DENV infections, and to test the efficacy of DENV vaccines and antivirals.
MeSH term(s)	Animals ; Chimera ; Dengue/immunology ; Dengue/prevention & control ; Dengue/virology ; Dengue Vaccines/immunology ; Dengue Virus/genetics ; Dengue Virus/immunology ; Dengue Virus/pathogenicity ; Disease Models, Animal ; Humans ; Mice/genetics ; Mice/immunology ; Mice/virology ; Mice, Inbred Strains ; Mice, SCID
Chemical Substances	Dengue Vaccines
Language	English
Publishing date	2008-07-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2008.06.010
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Article ; Online: Continuous glucose monitoring assessment of metabolic control in east African children and young adults with type 1 diabetes: A pilot and feasibility study.

McClure Yauch, Lauren / Velazquez, Eric / Piloya-Were, Thereza / Wainaina Mungai, Lucy / Omar, Anjumanara / Moran, Antoinette

Endocrinology, diabetes & metabolism

2020 Volume 3, Issue 3, Page(s) e00135

Abstract: Background: For individuals with type 1 diabetes (T1D) in East Africa and other low-income regions, the last decade has seen substantial gains in access to insulin and trained healthcare providers, yet metabolic control remains poor.: Methods: The ... ...

Abstract	Background: For individuals with type 1 diabetes (T1D) in East Africa and other low-income regions, the last decade has seen substantial gains in access to insulin and trained healthcare providers, yet metabolic control remains poor. Methods: The objective was to determine the feasibility of continuous glucose monitoring (CGM) and to gather baseline metabolic data for future power analysis in Ugandan and Kenyan youth with T1D using a Freestyle Libre Pro blinded CGM. Results: Of 78 participants recruited, four sensors fell off and six patients did not return, leaving 68 evaluable subjects. Average age was 16 ± 5 (range 4-26) years, 43% female. Average diabetes duration was 7 ± 5 years, insulin dose 0.9 ± 0.3 U/kg/d, and number of fingerstick glucose levels per day 2.1 ± 1.1. All were on human insulin. Point-of-care HbA1c was 10.9 ± 2.7% (96 ± 30 mmol/mol). Mean number of sensor days was 13 ± 3; >90% wore the sensor for ≥10 days. Mean glucose was 231 ± 86 mg/dL (12.8 ± 4.8 mmol/L). Only 30 ± 19% of time was spent in the target range (70-180 mg/dL; 3.9-10 mmol/L), and 7 ± 8% of time was spent in hypoglycaemia (glucose <55 mg/dL, 3.0 mmol/L). Hypoglycaemia occurred in 81% of participants, averaging five events/wk with an average duration of 140 ± 79 minutes/event. Conclusions: Despite significant diabetes care improvements, East African youth with T1D have poor metabolic control with chronic hyper- and hypoglycaemia, placing them at high risk for serious acute and chronic complications. This study demonstrates the feasibility of CGM use in this population and provides baseline metabolic data that will be used to inform a future intervention study.
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article
ISSN	2398-9238
ISSN (online)	2398-9238
DOI	10.1002/edm2.135
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Article ; Online: ISPAD Annual Conference 2019 Highlights.

Addala, Ananta / March, Christine / Marks, Brynn / Tommerdahl, Kalie / Shapiro, Jenna / Oyenusi, Elizabeth / Yauch, Lauren McClure / Goethals, Eveline R / Ahmad, Peerzada Ovais / Adhami, Sara / Ng, May / Ehtisham, Sarah / Agwu, Juliana Chizo

Pediatric diabetes

2020 Volume 21, Issue 2, Page(s) 152–157

MeSH term(s)	Animals ; Diabetes Complications ; Diabetes Mellitus, Type 1 ; Disease Management ; Humans
Language	English
Publishing date	2020-01-21
Publishing country	Denmark
Document type	Congress
ZDB-ID	1502504-4
ISSN	1399-5448 ; 1745-1426 ; 1399-543X
ISSN (online)	1399-5448
ISSN	1745-1426 ; 1399-543X
DOI	10.1111/pedi.12986
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Article ; Online: Direct inhibition of T-cell responses by the Cryptococcus capsular polysaccharide glucuronoxylomannan.

Yauch, Lauren E / Lam, Jennifer S / Levitz, Stuart M

PLoS pathogens

2006 Volume 2, Issue 11, Page(s) e120

Abstract: The major virulence factor of the pathogenic fungi Cryptococcus neoformans and C. gattii is the capsule. Glucuronoxylomannan (GXM), the major component of the capsule, is a high-molecular-weight polysaccharide that is shed during cryptococcosis and can ... ...

Abstract	The major virulence factor of the pathogenic fungi Cryptococcus neoformans and C. gattii is the capsule. Glucuronoxylomannan (GXM), the major component of the capsule, is a high-molecular-weight polysaccharide that is shed during cryptococcosis and can persist in patients after successful antifungal therapy. Due to the importance of T cells in the anticryptococcal response, we studied the effect of GXM on the ability of dendritic cells (DCs) to initiate a T-cell response. GXM inhibited the activation of cryptococcal mannoprotein-specific hybridoma T cells and the proliferation of OVA-specific OT-II T cells when murine bone marrow-derived DCs were used as antigen-presenting cells. Inhibition of OT-II T-cell proliferation was observed when either OVA protein or OVA323-339 peptide was used as antigen, indicating GXM did not merely prevent antigen uptake or processing. We found that DCs internalize GXM progressively over time; however, the suppressive effect did not require DCs, as GXM directly inhibited T-cell proliferation induced by anti-CD3 antibody, concanavalin A, or phorbol-12-myristate-13-acetate/ionomycin. Analysis of T-cell viability revealed that the reduced proliferation in the presence of GXM was not the result of increased cell death. GXM isolated from each of the four major cryptococcal serotypes inhibited the proliferation of human peripheral blood mononuclear cells stimulated with tetanus toxoid. Thus, we have defined a new mechanism by which GXM can impart virulence: direct inhibition of T-cell proliferation. In patients with cryptococcosis, this could impair optimal cell-mediated immune responses, thereby contributing to the persistence of cryptococcal infections.
MeSH term(s)	Animals ; Antigens, Fungal/pharmacology ; Bacterial Capsules/chemistry ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cryptococcus neoformans/metabolism ; Cryptococcus neoformans/pathogenicity ; Dendritic Cells/drug effects ; Dendritic Cells/metabolism ; Dose-Response Relationship, Drug ; Humans ; Mice ; Mice, Inbred C57BL ; Polysaccharides/metabolism ; Polysaccharides/pharmacology ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism
Chemical Substances	Antigens, Fungal ; Polysaccharides ; cryptococcal polysaccharide ; glucuronoxylomannan (76082-65-0)
Language	English
Publishing date	2006-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.0020120
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Article: Receptor-mediated clearance of Cryptococcus neoformans capsular polysaccharide in vivo.

Yauch, Lauren E / Mansour, Michael K / Levitz, Stuart M

Infection and immunity

2005 Volume 73, Issue 12, Page(s) 8429–8432

Abstract: Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is shed during cryptococcosis and taken up by macrophages. The roles of the putative GXM receptors CD14, CD18, Toll-like receptor 2 (TLR2), and TLR4 in GXM clearance from serum and deposition in ... ...

Abstract	Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is shed during cryptococcosis and taken up by macrophages. The roles of the putative GXM receptors CD14, CD18, Toll-like receptor 2 (TLR2), and TLR4 in GXM clearance from serum and deposition in the liver and spleen in receptor-deficient mice were studied. While alterations in the kinetics of GXM redistribution were seen in the mutant mice, none of the receptors was absolutely required for serum clearance or hepatosplenic accumulation.
MeSH term(s)	Animals ; Bacterial Capsules/chemistry ; Bacterial Capsules/metabolism ; Cryptococcosis/immunology ; Cryptococcosis/metabolism ; Cryptococcosis/parasitology ; Cryptococcus neoformans/pathogenicity ; Liver/metabolism ; Mice ; Mice, Mutant Strains ; Polysaccharides/analysis ; Polysaccharides/blood ; Polysaccharides/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/physiology ; Spleen/metabolism
Chemical Substances	Polysaccharides ; Receptors, Immunologic ; glucuronoxylomannan (76082-65-0)
Language	English
Publishing date	2005-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.73.12.8429-8432.2005
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Article ; Online: Trafficking and replication patterns reveal splenic macrophages as major targets of dengue virus in mice.

Prestwood, Tyler R / May, Monica M / Plummer, Emily M / Morar, Malika M / Yauch, Lauren E / Shresta, Sujan

Journal of virology

2012 Volume 86, Issue 22, Page(s) 12138–12147

Abstract: Human postmortem studies of natural dengue virus (DENV) infection have reported systemically distributed viral antigen. Although it is widely accepted that DENV infects mononuclear phagocytes, the sequence in which specific tissues and cell types are ... ...

Abstract	Human postmortem studies of natural dengue virus (DENV) infection have reported systemically distributed viral antigen. Although it is widely accepted that DENV infects mononuclear phagocytes, the sequence in which specific tissues and cell types are targeted remains uncharacterized. We previously reported that mice lacking alpha/beta and gamma interferon receptors permit high levels of DENV replication and show signs of systemic disease (T. R. Prestwood et al., J. Virol. 82:8411-8421, 2008). Here we demonstrate that within 6 h, DENV traffics to and replicates in both CD169(+) and SIGN-R1(+) macrophages of the splenic marginal zone or draining lymph node, respectively, following intravenous or intrafootpad inoculation. Subsequently, high levels of replication are detected in F4/80(+) splenic red pulp macrophages and in the bone marrow, lymph nodes, and Peyer's patches. Intravenously inoculated mice begin to succumb to dengue disease 72 h after infection, at which time viral replication occurs systemically, except in lymphoid tissues. In particular, high levels of replication occur in CD68(+) macrophages of the kidneys, heart, thymus, and gastrointestinal tract. Over the course of infection, proportionately large quantities of DENV traffic to the liver and spleen. However, late during infection, viral trafficking to the spleen decreases, while trafficking to the liver, thymus, and kidneys increases. The present study demonstrates that macrophage populations, initially in the spleen and other lymphoid tissues and later in nonlymphoid tissues, are major targets of DENV infection in vivo.
MeSH term(s)	Animals ; Biological Transport ; Bone Marrow/virology ; CD58 Antigens/biosynthesis ; Cell Adhesion Molecules/biosynthesis ; Dengue/metabolism ; Dengue/virology ; Dengue Virus/metabolism ; Immunohistochemistry/methods ; Kinetics ; Lectins, C-Type/biosynthesis ; Lymph Nodes/virology ; Macrophages/cytology ; Macrophages/virology ; Mice ; Peyer's Patches/virology ; Receptors, Cell Surface/biosynthesis ; Sialic Acid Binding Ig-like Lectin 1/biosynthesis ; Spleen/cytology ; Spleen/virology ; Tissue Distribution ; Virus Replication
Chemical Substances	CD58 Antigens ; Cell Adhesion Molecules ; DC-specific ICAM-3 grabbing nonintegrin ; Lectins, C-Type ; Receptors, Cell Surface ; Sialic Acid Binding Ig-like Lectin 1
Language	English
Publishing date	2012-08-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00375-12
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Article ; Online: Gamma interferon (IFN-γ) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-α/β receptor-deficient mice.

Prestwood, Tyler R / Morar, Malika M / Zellweger, Raphaël M / Miller, Robyn / May, Monica M / Yauch, Lauren E / Lada, Steven M / Shresta, Sujan

Journal of virology

2012 Volume 86, Issue 23, Page(s) 12561–12570

Abstract: We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/βR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR ... ...

Abstract	We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/βR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR alone and virtually no mice lacking the IFN-α/βR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-α/βR, signaling through the IFN-γR confers approximately 140-fold greater resistance against systemic vascular leakage-associated dengue disease and virtually complete protection from dengue-induced paralysis. Viral replication in the spleen was assessed by immunohistochemistry and flow cytometry, which revealed a reduction in the number of infected cells due to IFN-γR signaling by 2 days after infection, coincident with elevated levels of IFN-γ in the spleen and serum. By 4 days after infection, IFN-γR signaling was found to restrict DENV replication systemically. Clearance of DENV, on the other hand, occurred in the absence of IFN-γR, except in the central nervous system (CNS) (brain and spinal cord), where clearance relied on IFN-γ from CD8(+) T cells. These results demonstrate the roles of IFN-γR signaling in protection from initial systemic and subsequent CNS disease following DENV infection and demonstrate the importance of CD8(+) T cells in preventing DENV-induced CNS disease.
MeSH term(s)	Adoptive Transfer ; Analysis of Variance ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Central Nervous System/immunology ; Central Nervous System/virology ; Dengue/complications ; Dengue/immunology ; Dengue/pathology ; Dengue Virus/physiology ; Disease Susceptibility/immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunohistochemistry ; Interferon-gamma/blood ; Interferon-gamma/metabolism ; Mice ; Mice, Mutant Strains ; Paralysis/etiology ; Paralysis/immunology ; Real-Time Polymerase Chain Reaction ; Receptor, Interferon alpha-beta/genetics ; Receptors, Interferon/metabolism ; Regression Analysis ; Signal Transduction/physiology ; Spleen/virology ; Virus Replication/physiology ; Interferon gamma Receptor
Chemical Substances	Receptors, Interferon ; Receptor, Interferon alpha-beta (156986-95-7) ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2012-09-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.06743-11
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Article: Opsonic requirements for dendritic cell-mediated responses to Cryptococcus neoformans.

Kelly, Ryan M / Chen, Jianmin / Yauch, Lauren E / Levitz, Stuart M

Infection and immunity

2005 Volume 73, Issue 1, Page(s) 592–598

Abstract: The encapsulated pathogenic yeast Cryptococcus neoformans is poorly recognized by phagocytic cells in the absence of opsonins. Macrophages will bind and internalize complement- or antibody-opsonized C. neoformans; however, less is known about the role of ...

Abstract	The encapsulated pathogenic yeast Cryptococcus neoformans is poorly recognized by phagocytic cells in the absence of opsonins. Macrophages will bind and internalize complement- or antibody-opsonized C. neoformans; however, less is known about the role of opsonins in dendritic cell (DC)-mediated recognition of the organism. Thus, we studied the opsonic requirements for binding to C. neoformans by cultured human monocyte-derived and murine bone marrow-derived DCs and whether binding leads to antifungal activity and cytokine release. Binding of unopsonized C. neoformans to human and murine DCs was negligible. Opsonization with pooled human serum (PHS) increased binding, while heat treatment of PHS virtually abolished this binding, thus suggesting a role for heat-labile complement components. PHS plus a monoclonal anticapsular antibody, 3C2, had an additive effect on binding for most cryptococcal strains. Human and murine DCs exhibited pronounced anticryptococcal activity in the presence of the antibody at early (2-h) and late (24-h) time points; however, PHS opsonization did not supplement this anticryptococcal activity. Antifungal activity against C. neoformans opsonized in PHS and/or antibody was partially reduced in the presence of inhibitors of the respiratory burst response. Human, but not murine, DCs released modest amounts of tumor necrosis factor alpha when stimulated with C. neoformans opsonized in PHS and/or antibody. However, opsonized C. neoformans failed to stimulate detectable release of interleukin 10 (IL-10) or IL-12p70 from either DC population. Thus, human and murine DCs show maximal binding to and antifungal activity against C. neoformans via a process highly dependent on opsonization.
MeSH term(s)	Animals ; Cryptococcus neoformans/immunology ; Cytokines/biosynthesis ; Dendritic Cells/immunology ; Humans ; Mice ; Mice, Inbred C57BL ; Phagocytosis ; Respiratory Burst ; Tumor Necrosis Factor-alpha/physiology
Chemical Substances	Cytokines ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2005-01
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.73.1.592-598.2005
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