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https://www.readbyqxmd.com/read/28444391/dual-display-phage-selection-driven-by-co-engagement-of-two-targets-by-two-different-antibody-fragments
#1
Séverine Fagète, Ledicia Botas-Perez, Irène Rossito-Borlat, Kenneth Adea, Franck Gueneau, Ulla Ravn, François Rousseau, Marie Kosco-Vilbois, Nicolas Fischer, Oliver Hartley
Antibody phage display technology has supported the emergence of numerous therapeutic antibodies. The development of bispecific antibodies, a promising new frontier in antibody therapy, could be facilitated by new phage display approaches that enable pairs of antibodies to be co-selected based on co-engagement of their respective targets. We describe such an approach, making use of two complementary leucine zipper domains that heterodimerize with high affinity. Phagemids encoding a first antibody fragment (scFv) fused to phage coat protein via the first leucine zipper are rescued in bacteria expressing a second scFv fused to the second leucine zipper as a soluble periplasmic protein, so that it is acquired by phage during assembly...
April 24, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28443132/disease-resistance-and-the-definition-of-genetic-enhancement
#2
Derek So, Erika Kleiderman, Seydina B Touré, Yann Joly
Recent gene editing experiments carried out in human embryos have raised the question of whether interventions like the introduction of a CCR5-Δ32 deletion, which could provide heritable resistance to HIV infection, ought to be considered enhancements. Many authors have used the term "enhancement" in different ways, some based on patients' biomedical outcomes and others on their social context. These classifications are often considered overly imprecise. Nevertheless, the concept of "enhancement" could affect the ways in which these applications are regulated in different jurisdictions, the availability of coverage by insurers or public health care, and the force of public opinion in shaping future policy on gene editing...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28432326/a-novel-mechanism-linking-memory-stem-cells-with-innate-immunity-in-protection-against-hiv-1-infection
#3
Yufei Wang, Trevor Whittall, Stuart Neil, Gary Britton, Mukesh Mistry, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Jaranit Kaewkungwal, Sorachai Nitayaphan, Xuesong Yu, Alicia Sato, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Jerome H Kim, Thomas Lehner
HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4(+) T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431923/sources-of-racial-disparities-in-hiv-prevalence-in-men-who-have-sex-with-men-in-atlanta-ga-usa-a-modelling-study
#4
Steven M Goodreau, Eli S Rosenberg, Samuel M Jenness, Nicole Luisi, Sarah E Stansfield, Gregorio A Millett, Patrick S Sullivan
BACKGROUND: In the USA, men who have sex men (MSM) are at high risk for HIV, and black MSM have a substantially higher prevalence of infection than white MSM. We created a simulation model to assess the strength of existing hypotheses and data that account for these disparities. METHODS: We built a dynamic, stochastic, agent-based network model of black and white MSM aged 18-39 years in Atlanta, GA, USA, that incorporated race-specific individual and dyadic-level prevention and risk behaviours, network attributes, and care patterns...
April 18, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28424283/simian-immunodeficiency-virus-targeting-of-cxcr3-cd4-t-cells-in-secondary-lymphoid-organs-is-associated-with-robust-cxcl10-expression-in-monocyte-macrophage-subsets
#5
Masayuki Fujino, Hirotaka Sato, Tomotaka Okamura, Akihiko Uda, Satoshi Takeda, Nursarat Ahmed, Shigeyuki Shichino, Teiichiro Shiino, Yohei Saito, Satoru Watanabe, Chie Sugimoto, Marcelo Kuroda, Manabu Ato, Yoshiyuki Nagai, Shuji Izumo, Kouji Matsushima, Masaaki Miyazawa, Aftab A Ansari, Francois Villinger, Kazuyasu Mori
Glycosylation of Env defines pathogenic properties of SIV. We previously demonstrated that pathogenic SIVmac239 and live-attenuated, quintuple deglycosylated Env mutant (Δ5G) target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012). Herein, we studied the host responses relevant to SIV targeting of CXCR3(+)CCR5(+) CD4(+) T cells in SLOs...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#6
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421534/immune-alterations-in-cd8-t-cells-are-associated-with-neuronal-c-c-and-c-x-c-chemokine-receptor-regulation-through-adenosine-a2a-receptor-signaling-in-a-btbr-t-itpr3-tf-j-autistic-mouse-model
#7
Sheikh F Ahmad, Mushtaq A Ansari, Ahmed Nadeem, Saleh A Bakheet, Raish Mohammad, Sabry M Attia
Associative studies on a range of neurodevelopmental disorders have identified relationships between behavioral deficits and immune system function. The BTBR T(+) Itpr3(tf)/J (BTBR) mouse strain displays aberrant characteristics in its social behavior and immune responses, providing a significant opportunity to examine the relationship between behavior and the immune system. This study investigated the influence of adenosine A2A receptor activity on C-C and C-X-C chemokine receptors involved in autism in the BTBR mouse model...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28416485/targeting-autocrine-ccl5-ccr5-axis-reprograms-immunosuppressive-myeloid-cells-and-reinvigorates-antitumor-immunity
#8
Yi Ban, Junhua Mai, Xin Li, Marisa Mitchell-Flack, Tuo Zhang, Lixing Zhang, Lotfi Chouchane, Mauro Ferrari, Haifa Shen, Xiaojing Ma
The tumor-promoting potential of CCL5 has been proposed but remains poorly understood. We demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. The absence of the autocrine CCL5 abrogated the generation of granulocytic myeloid-derived suppressor cells and tumor-associated macrophages. In parallel, enhanced maturation of intratumoral neutrophils and macrophages occurred in spite of tumor-derived CCL5. The refractory nature of ccl5-null myeloid precursors to tumor-derived CCL5 was attributable to their persistent lack of membrane-bound CCR5...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28414206/wenshen-zhuanggu-formula-effectively-suppresses-breast-cancer-bone-metastases-in-a-mouse-xenograft-model
#9
Jia-Jia Li, Wei-Ling Chen, Jian-Yi Wang, Qian-Wen Hu, Zhen-Ping Sun, Shuai Zhang, Sheng Liu, Xiang-Hui Han
Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA-MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice...
April 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28413739/genetic-modulation-therapy-through-stem-cell-transplantation-for-human-immunodeficiency-virus-1-infection
#10
REVIEW
Varshil Mehta, Divya Chandramohan, Shivika Agarwal
Highly active anti-retroviral treatment has changed the dimensions of the outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment which is spreading throughout the world extensively. Given the confinements of the present restorative methodologies and the non-availability of any strategic vaccination against HIV, there is a squeezing need to build a therapeutic treatment. Viral tropism for HIV includes CD4+ cells, macrophages, and microglial cells, and it is through binding with co-receptors C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4)...
March 13, 2017: Curēus
https://www.readbyqxmd.com/read/28413625/hiv-associated-neurocognitive-disorders-recent-advances-in-pathogenesis-biomarkers-and-treatment
#11
REVIEW
Antonia Carroll, Bruce Brew
HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the "gold standard" of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND...
2017: F1000Research
https://www.readbyqxmd.com/read/28405623/bcg-vaccination-induces-hiv-target-cell-activation-in-hiv-exposed-infants-in-a-randomized-trial
#12
Melanie A Gasper, Anneke C Hesseling, Isaac Mohar, Landon Myer, Tali Azenkot, Jo-Ann S Passmore, Willem Hanekom, Mark F Cotton, I Nicholas Crispe, Donald L Sodora, Heather B Jaspan
BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4(+) T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28398593/ccr5-expression-haplotype-and-immune-activation-in-protection-from-infection-in-hiv-exposed-uninfected-individuals-in-hiv-serodiscordant-relationships
#13
Shameem Z Jaumdally, Anabela Picton, Caroline T Tiemessen, Maria Paximadis, Heather B Jaspan, Hoyam Gamieldien, Lindi Masson, David Coetzee, Anna-Lise Williamson, Francesca Little, Pamela P Gumbi, Jo-Ann S Passmore
BACKGROUND: Several host factors have been implicated in resistance to HIV infection in individuals who remain HIV-seronegative despite exposure. In a cohort of HIV-serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T-cell activation in resistance to HIV infection. METHODS: Males and females in stable long-term relationships with either HIV-infected or uninfected partners were recruited, blood T-cell activation (CD38, HLA-DR, CCR5 and Ki67) and plasma cytokine concentrations were evaluated...
April 11, 2017: Immunology
https://www.readbyqxmd.com/read/28392642/the-contributory-roles-of-th17-lymphocyte-and-cytotoxic-t-lymphocyte-at-the-hair-bulge-region-as-well-as-the-hair-bulb-area-in-the-chronic-alopecia-areata-patients
#14
Jin-Woo Hong, Chae-Young Lee, Seung-Min Ha, Seung-Hwan Choi, Tae-Hoon Kim, Ki-Hoon Song, Ki-Ho Kim
BACKGROUND: Alopecia areata (AA) is a T cell-mediated autoimmune disease that targets hair follicles and interrupts hair regrowth. The microenvironment of the effector T cells and their related cytokines may affect immunopathogenesis around the hair bulb/bulge. OBJECTIVE: To determine the contributory roles of the effector T cell subsets and related cytokines to the pathogenesis of AA. METHODS: We investigated the correlation between histopathological grades and four clinical prognostic factors in 331 patients with AA, and analyzed the topography of T cell infiltrates and related cytokines around the hair bulb/bulge according to histopathological grades through immunohistochemical and double immunofluorescence studies on a subset of AA specimens...
April 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28388241/chagas-disease-immunogenetics-elusive-markers-of-disease-progression
#15
Yelenca Ortega Zamora, Leidy Johana Escamilla Rojas, Elvis Mayron Villa Sandoval, Joan Steven Vela Porras, Edgar Yarleison Cossio Contrera, Sergio Sebastian Cubides Romero, Pedro David Carreño Ramirez, Hermes Urriago Losada, Carolina De Los Rios, Daniela Alejandra Gomez Mahecha, Karen Daniela Lovera Serrano, Juan Carlos Barreto Montaña, Viviana Lorena Narvaez Caicedo, Fredy Rs Gutierrez
Chagas disease (CD) is caused by a parasitic infection. The disease usually occurs after decades of the primary infection and can involve the myocardium or the digestive system. Of note, around 30% of T. cruzi infected patients develop CD while the other 70% may remain asymptomatic for their entire life. CD is usually observed as familial clustered phenomena. Moreover, individuals with chronic Chagas heart disease (CCHD) usually present a strong, deregulated immune response, which strongly suggests an immunogenetic effect...
April 7, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28387899/a-correlation-study-between-gene-polymorphism-of-th-cell-expressed-chemokine-receptor-cxcr3-and-its-ligand-levels-with-hcv-infection-prognosis
#16
Y Lu, L-Y Lin, J-G Tan, H-P Deng, X-H Li, Z Zhang, Y Li, Z Zhou, X Xu, X Xie, S-J Mei
OBJECTIVE: Chemokine receptor and its ligand participate in viral immunity and HCV infection, which are important inflammatory mediators. The current study showed the different roles of Th cell secreted chemokines CXCR3, CCR5 and CCR6 in chronic liver inflammation after HCV infection. As one important chemokine receptor, the role of polypeptide property and ligand level in HCV prognosis is still unclear. This study aims to investigate gene polymorphism of chemokine genes and ligand level, and their correlation with patient liver function, to provide evidence for HCV prognosis and chronic transition mechanism...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28385330/a-similar-local-immune-and-oxidative-stress-phenotype-in-vitiligo-and-halo-nevus
#17
Yuqi Yang, Shuli Li, Guannan Zhu, Qian Zhang, Gang Wang, Tianwen Gao, Chunying Li, Lin Wang, Zhe Jian
BACKGROUND: Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood. OBJECTIVE: The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response. METHODS: Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry...
March 19, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28382399/ccr5-in-recruitment-and-activation-of-myeloid-derived-suppressor-cells-in-melanoma
#18
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
Malignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Using ret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment...
April 5, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28360890/driving-hiv-1-into-a-vulnerable-corner-by-taking-advantage-of-viral-adaptation-and-evolution
#19
REVIEW
Shigeyoshi Harada, Kazuhisa Yoshimura
Anti-retroviral therapy (ART) is crucial for controlling human immunodeficiency virus type-1 (HIV-1) infection. Recently, progress in identifying and characterizing highly potent broadly neutralizing antibodies has provided valuable templates for HIV-1 therapy and vaccine design. Nevertheless, HIV-1, like many RNA viruses, exhibits genetically diverse populations known as quasispecies. Evolution of quasispecies can occur rapidly in response to selective pressures, such as that exerted by ART and the immune system...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28358741/novel-genetic-associations-and-gene-gene-interactions-of-chemokine-receptor-and-chemokine-genetic-polymorphisms-in-hiv-aids
#20
Jacqueline M Valverde-Villegas, Rúbia Marília De Medeiros, Karine Pereira de Andrade, Vanessa Cristina Jacovas, Breno Riegel Dos Santos, Daniel Simon, Sabrina Esteves de Matos Almeida, José Artur Bogo Chies
OBJECTIVE: To investigate the influence of candidate polymorphisms on chemokine receptor/ligand genes on HIV infection and AIDS progression (HIV/AIDS). DESIGN: Fifteen polymorphisms of the CCR3, CCR4, CCR5, CCR6, CCR8, CXCR3, CXCR6, CCL20, CCL22 and CXCL10 genes were analysed in 206 HIV-positive subjects classified as rapid progressors (RPs; n = 40), or non-RPs (NRPs; n = 166) and in 294 HIV-seronegative subjects. METHODS: The polymorphisms were genotyped using minisequencing...
March 29, 2017: AIDS
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