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Cold Spring Harbor Perspectives in Biology

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https://www.readbyqxmd.com/read/28716894/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-the-risks-of-incomplete-immunity-to-dengue-virus-revealed-by-vaccination
#1
Stephen S Whitehead, Kanta Subbarao
Immune enhancement of dengue disease continues to be a concern for those with incomplete immunity in endemic areas. Advanced testing and follow-up of a newly available live attenuated dengue vaccine has recently shown the ability of vaccination to predispose some recipients for a severe outcome on subsequent infection. To improve safety, recommendations have been made to restrict use of the vaccine to those who are likely to have had prior exposure to dengue virus (DENV). Researchers continue to investigate dengue immunity and seek evidence that dengue vaccines can be safely administered to all populations needing protection...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716893/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-there-is-only-one-true-winner
#2
Scott B Halstead
The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716892/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-questions-raised-by-the-development-and-implementation-of-dengue-vaccines-example-of-the-sanofi-pasteur-tetravalent-dengue-vaccine
#3
Bruno Guy
Dengue is a still-growing public health concern in many tropical and subtropical regions of the world. The development and implementation of an effective dengue vaccine in these regions is a high priority. This insight focuses on the expected characteristics of a safe and efficacious vaccine, referring to the clinical experience obtained during the development of the first tetravalent dengue vaccine from Sanofi Pasteur, now licensed in several endemic countries. Safety and efficacy data from both short- and long-term follow-up of large-scale efficacy studies will be discussed, as well as the next steps following vaccine introduction...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716891/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-the-path-to-a-dengue-vaccine-learning-from-human-natural-dengue-infection-studies-and-vaccine-trials
#4
Aravinda M de Silva, Eva Harris
Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716890/negative-regulation-of-cytokine-signaling-in-immunity
#5
Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko Nakatsukasa
Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716889/cytokines-transcription-factors-and-the-initiation-of-t-cell-development
#6
Hiroyuki Hosokawa, Ellen V Rothenberg
Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716888/interleukin-il-12-and-il-23-and-their-conflicting-roles-in-cancer
#7
Juming Yan, Mark J Smyth, Michele W L Teng
The balance of proinflammatory cytokines interleukin (IL)-12 and IL-23 plays a key role in shaping the development of antitumor or protumor immunity. In this review, we discuss the role IL-12 and IL-23 plays in tumor biology from preclinical and clinical data. In particular, we discuss the mechanism by which IL-23 promotes tumor growth and metastases and how the IL-12/IL-23 axis of inflammation can be targeted for cancer therapy.
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716887/cell-cell-contact-and-receptor-tyrosine-kinase-signaling
#8
Christine Chiasson-MacKenzie, Andrea I McClatchey
The behavior of cells within tissues is governed by the activities of adhesion receptors that provide spatial cues and transmit forces through intercellular junctions, and by growth-factor receptors, particularly receptor tyrosine kinases (RTKs), that respond to biochemical signals from the environment. Coordination of these two activities is essential for the patterning and polarized migration of cells during morphogenesis and for homeostasis in mature tissues; loss of this coordination is a hallmark of developing cancer and driver of metastatic progression...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716886/clinical-neurology-and-epidemiology-of-the-major-neurodegenerative-diseases
#9
Michael G Erkkinen, Mee-Ohk Kim, Michael D Geschwind
Neurodegenerative diseases are a common cause of morbidity and cognitive impairment in older adults. Most clinicians who care for the elderly are not trained to diagnose these conditions, perhaps other than typical Alzheimer's disease (AD). Each of these disorders has varied epidemiology, clinical symptomatology, laboratory and neuroimaging features, neuropathology, and management. Thus, it is important that clinicians be able to differentiate and diagnose these conditions accurately. This review summarizes and highlights clinical aspects of several of the most commonly encountered neurodegenerative diseases, including AD, frontotemporal dementia (FTD) and its variants, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Huntington's disease (HD)...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716885/cytokines-and-long-noncoding-rnas
#10
Susan Carpenter, Katherine A Fitzgerald
Cytokines and long noncoding RNAs (lncRNAs) are intertwined in the regulatory circuit controlling immunity. lncRNA expression levels are altered following cytokine stimulation in a cell-type-specific fashion. lncRNAs, in turn, regulate the inducible expression of cytokines following immune activation. These studies position lncRNAs as important regulators of gene expression within the complex pathways of the immune system. Our understanding of the functions of lncRNAs is just beginning. Current methodologies for functionally understanding how these transcripts mediate their effects are unable to keep up with the speed of genomic outputs cataloging thousands of these novel genes...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716884/which-dengue-vaccine-approach-is-the-most-promising-and-should-we-be-concerned-about-enhanced-disease-after-vaccination-the-challenges-of-a-dengue-vaccine
#11
Gavin Screaton, Juthathip Mongkolsapaya
A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716883/role-of-the-%C3%AE-common-%C3%AE-c-family-of-cytokines-in-health-and-disease
#12
Timothy R Hercus, Winnie L T Kan, Sophie E Broughton, Denis Tvorogov, Hayley S Ramshaw, Jarrod J Sandow, Tracy L Nero, Urmi Dhagat, Emma J Thompson, Karen S Cheung Tung Shing, Duncan R McKenzie, Nicholas J Wilson, Catherine M Owczarek, Gino Vairo, Andrew D Nash, Vinay Tergaonkar, Timothy Hughes, Paul G Ekert, Michael S Samuel, Claudine S Bonder, Michele A Grimbaldeston, Michael W Parker, Angel F Lopez
The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28663210/is-it-possible-to-develop-a-universal-influenza-virus-vaccine-outflanking-antibody-immunodominance-on-the-road-to-universal-influenza-vaccination
#13
Davide Angeletti, Jonathan W Yewdell
Influenza remains a major human pathogen despite seasonal vaccination. At long last, there is energy and resources to develop influenza vaccines that provide more predictable and durable protection. Vaccines based on inducing antibodies to the conserved stem of the viral hemagglutinin (HA) have emerged as leading candidates for broadening population immunity and ultimately limiting antigenic drift. Here, we discuss the knowns and unknowns of HA-specific B-cell and antibody responses. In particular, we focus on how immunodominance sculpts antibody responses and drives antigenic drift...
June 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28663209/is-it-possible-to-develop-a-universal-influenza-virus-vaccine-toward-a-universal-influenza-virus-vaccine-potential-target-antigens-and-critical-aspects-for-vaccine-development
#14
Florian Krammer, Adolfo García-Sastre, Peter Palese
Influenza viruses cause seasonal epidemics as well as pandemics and are a significant concern for human health. Current influenza virus vaccines show efficacy when they are antigenically well matched to circulating strains. Seasonal influenza viruses undergo antigenic drift at a high rate and, therefore, current vaccines have to be reformulated and readministered on an annual basis. Mismatches between vaccine strains and circulating strains frequently occur, significantly decreasing vaccine efficacy. In addition, current seasonal influenza virus vaccines have limited efficacy against newly emerging pandemic viruses...
June 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28663208/is-it-possible-to-develop-a-universal-influenza-virus-vaccine-potential-for-a-universal-influenza-vaccine
#15
James E Crowe
Development of optimal vaccines for influenza is challenging, in part as a result of the high antigenic variability in field strains associated with genetic shift from reassortment and genetic drift from point mutations. Discovery of conserved antigenic sites on the hemagglutinin (HA) protein for neutralizing antibodies suggested the possibility that influenza vaccines could be developed that induce focused antibody responses to the conserved neutralizing determinants, especially the HA stem region. Recent studies have focused on the antigenicity and immunogenicity of such domains, using monoclonal antibodies and candidate-engineered HA stem-based vaccines...
June 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28663207/is-it-possible-to-develop-a-universal-influenza-virus-vaccine-immunogenetic-considerations-underlying-b-cell-biology-in-the-development-of-a-pan-subtype-influenza-a-vaccine-targeting-the-hemagglutinin-stem
#16
Sarah F Andrews, Barney S Graham, John R Mascola, Adrian B McDermott
Current influenza vaccines preferentially generate B-cell responses to the variable hemagglutinin (HA) head. Focusing vaccine-induced antibody responses on epitopes in the conserved HA stem may provide better protection against future drifted and pandemic strains. Understanding the basis for the dominant HA head and subdominant HA stem-specific responses at the level of B-cell activation and differentiation will be critical for designing vaccines that induce sustained stem-specific responses. Identifying antibody lineages with broad neutralizing activity against influenza A viruses and defining the structural mode of recognition for germline precursors of those antibodies will also guide future immunogen design...
June 29, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630079/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-lessons-from-the-antibody-response-to-hiv-1
#17
Gabriel D Victora, Hugo Mouquet
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630078/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-a-role-for-antibody-feedback
#18
Kai-Michael Toellner, Daniel M-Y Sze, Yang Zhang
We discuss the impact of antibody feedback on affinity maturation of B cells. Competition from epitope-specific antibodies produced earlier during the immune response leads to immune complex formation, which is essential for transport and deposition of antigen onto follicular dendritic cells (FDCs). It also reduces the concentration of free epitopes into the μm to nm range, which is essential for B-cell receptors (BCRs) to sense affinity-dependent changes in binding capacity. Antibody feedback may also induce epitope spreading, leading to a broader selection of epitopes recognized by newly emerging B-cell clones...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630077/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-breaking-through-immunity-s-glass-ceiling
#19
Garnett Kelsoe, Barton F Haynes
A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28630076/what-are-the-primary-limitations-in-b-cell-affinity-maturation-and-how-much-affinity-maturation-can-we-drive-with-vaccination-is-affinity-maturation-a-self-defeating-process-for-eliciting-broad-protection
#20
Christopher T Stamper, Patrick C Wilson
Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells...
June 19, 2017: Cold Spring Harbor Perspectives in Biology
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