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https://www.readbyqxmd.com/read/28732035/vaccine-induced-immune-responses-against-both-gag-and-env-improve-control-of-simian-immunodeficiency-virus-replication-in-rectally-challenged-rhesus-macaques
#1
Mauricio A Martins, Young C Shin, Lucas Gonzalez-Nieto, Aline Domingues, Martin J Gutman, Helen S Maxwell, Iris Castro, Diogo M Magnani, Michael Ricciardi, Nuria Pedreño-Lopez, Varian Bailey, Dillon Betancourt, John D Altman, Matthias Pauthner, Dennis R Burton, Benjamin von Bredow, David T Evans, Maoli Yuan, Christopher L Parks, Keisuke Ejima, David B Allison, Eva Rakasz, Glen N Barber, Saverio Capuano, Jeffrey D Lifson, Ronald C Desrosiers, David I Watkins
The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4)...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730622/susceptibility-to-hiv-1-infection-is-influenced-by-toll-like-receptor-2-196-to-174-polymorphism-in-north-indian-population
#2
Sanjukta Vidyant, Animesh Chatterjee, Vikas Agarwal, Tapan N Dhole
INTRODUCTION: Toll like receptors (TLRs) are pattern recognition receptors, recognize molecular patterns of pathogens and play an important role in innate immunity. Recent studies have identified that single nucleotide polymorphism (SNPs) in TLR gene impairs the response to TLR ligands in some individuals and is associated with susceptibility to various infectious diseases. AIM: The aim of the present study is to investigate the role of four SNPs in the TLR2 gene, -196 to -174 Ins/Del, 2258 G/A (Arg753Gln), 2029 C/T (Arg677Trp) and 1892 C/A (Pro631His) with susceptibility and progression to HIV-1 in North Indian individuals...
July 20, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28728075/immunological-tolerance-as-a-barrier-to-protective-hiv-humoral-immunity
#3
REVIEW
Kristin Ms Schroeder, Amanda Agazio, Raul M Torres
HIV-1 infection typically eludes antibody control by our immune system and is not yet prevented by a vaccine. While many viral features contribute to this immune evasion, broadly neutralizing antibodies (bnAbs) against HIV-1 are often autoreactive and it has been suggested that immunological tolerance may restrict a neutralizing antibody response. Indeed, recent Ig knockin mouse studies have shown that bnAb-expressing B cells are largely censored by central tolerance in the bone marrow. However, the contribution of peripheral tolerance in limiting the HIV antibody response by anergic and potentially protective B cells is poorly understood...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28726771/rapid-elicitation-of-broadly-neutralizing-antibodies-to-hiv-by-immunization-in-cows
#4
Devin Sok, Khoa M Le, Melissa Vadnais, Karen Saye-Francisco, Joseph G Jardine, Jonathan Torres, Zachary T Berndsen, Leopold Kong, Robyn Stanfield, Jennifer Ruiz, Alejandra Ramos, Chi-Hui Liang, Patricia L Chen, Michael F Criscitiello, Waithaka Mwangi, Ian A Wilson, Andrew B Ward, Vaughn V Smider, Dennis R Burton
No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)(1) have improved the elicitation of potent isolate-specific antibody responses in rabbits(2) and macaques(3), but so far failed to induce broadly neutralizing antibodies. One possible contributor to this failure is that the relevant antibody repertoires are poorly suited to target somewhat occluded conserved epitope regions on Env relative to exposed variable epitopes...
July 20, 2017: Nature
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#5
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#6
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28720097/a-versatile-papaya-mosaic-virus-papmv-vaccine-platform-based-on-sortase-mediated-antigen-coupling
#7
Ariane Thérien, Mikaël Bédard, Damien Carignan, Gervais Rioux, Louis Gauthier-Landry, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Pierre Savard, Denis Leclerc
BACKGROUND: Flexuous rod-shaped nanoparticles made of the coat protein (CP) of papaya mosaic virus (PapMV) have been shown to trigger innate immunity through engagement of toll-like receptor 7 (TLR7). PapMV nanoparticles can also serve as a vaccine platform as they can increase the immune response to fused peptide antigens. Although this approach shows great potential, fusion of antigens directly to the CP open reading frame (ORF) is challenging because the fused peptides can alter the structure of the CP and its capacity to self assemble into nanoparticles-a property essential for triggering an efficient immune response to the peptide...
July 18, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#8
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28717654/fusion-to-flaviviral-leader-peptide-targets-hiv-1-reverse-transcriptase-for-secretion-and-reduces-its-enzymatic-activity-and-ability-to-induce-oxidative-stress-but-has-no-major-effects-on-its-immunogenic-performance-in-dna-immunized-mice
#9
Anastasia Latanova, Stefan Petkov, Yulia Kuzmenko, Athina Kilpeläinen, Alexander Ivanov, Olga Smirnova, Olga Krotova, Sergey Korolev, Jorma Hinkula, Vadim Karpov, Maria Isaguliants, Elizaveta Starodubova
Reverse transcriptase (RT) is a key enzyme in viral replication and susceptibility to ART and a crucial target of immunotherapy against drug-resistant HIV-1. RT induces oxidative stress which undermines the attempts to make it immunogenic. We hypothesized that artificial secretion may reduce the stress and make RT more immunogenic. Inactivated multidrug-resistant RT (RT1.14opt-in) was N-terminally fused to the signal providing secretion of NS1 protein of TBEV (Ld) generating optimized inactivated Ld-carrying enzyme RT1...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28714868/interval-dosing-with-the-hdac-inhibitor-vorinostat-effectively-reverses-hiv-latency
#10
Nancie M Archin, Jennifer L Kirchherr, Julia Am Sung, Genevieve Clutton, Katherine Sholtis, Yinyan Xu, Brigitte Allard, Erin Stuelke, Angela D Kashuba, Joann D Kuruc, Joseph Eron, Cynthia L Gay, Nilu Goonetilleke, David M Margolis
BACKGROUND: The histone deacetylase (HDAC) inhibitor vorinostat (VOR) can increase HIV RNA expression in vivo within resting CD4+ T cells of aviremic HIV+ individuals. However, while studies of VOR or other HDAC inhibitors have reported reversal of latency, none has demonstrated clearance of latent infection. We sought to identify the optimal dosing of VOR for effective serial reversal of HIV latency. METHODS: In a study of 16 HIV-infected, aviremic individuals, we measured resting CD4+ T cell-associated HIV RNA ex vivo and in vivo following a single exposure to VOR, and then in vivo after a pair of doses separated by 48 or 72 hours, and finally following a series of 10 doses given at 72-hour intervals...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28713376/myristoylation-an-important-protein-modification-in-the-immune-response
#11
REVIEW
Daniel Ikenna Udenwobele, Ruey-Chyi Su, Sara V Good, Terry Blake Ball, Shailly Varma Shrivastav, Anuraag Shrivastav
Protein N-myristoylation is a cotranslational lipidic modification specific to the alpha-amino group of an N-terminal glycine residue of many eukaryotic and viral proteins. The ubiquitous eukaryotic enzyme, N-myristoyltransferase, catalyzes the myristoylation process. Precisely, attachment of a myristoyl group increases specific protein-protein interactions leading to subcellular localization of myristoylated proteins with its signaling partners. The birth of the field of myristoylation, a little over three decades ago, has led to the understanding of the significance of protein myristoylation in regulating cellular signaling pathways in several biological processes especially in carcinogenesis and more recently immune function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713371/regulation-of-subunit-specific-germinal-center-b-cell-responses-to-the-hiv-1-envelope-glycoproteins-by-antibody-mediated-feedback
#12
Mattias N E Forsell, Linda Kvastad, Saikiran K Sedimbi, John Andersson, Mikael C I Karlsson
The regulation of germinal center (GC) B cell responses to single epitopes is well investigated. How monoclonal B cells are regulated within the polyclonal B cell response to protein antigens is less so. Here, we investigate the primary GC B cell response after injection of mice with HIV-1 envelope glycoproteins. We demonstrate that single GCs are seeded by a diverse number of B cell clones shortly after a single immunization and that the presence of Env-specific antibodies can inhibit the development of early GC B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28713164/human-immunodeficiency-virus-type-1-induces-a-regulatory-b-cell-like-phenotype-in-vitro
#13
Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Maria-Ángeles Muñoz-Fernandez, Rafael Correa-Rocha, Marjorie Pion
Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells...
July 17, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28710608/vaccine-platform-recombinant-measles-virus
#14
REVIEW
Michael D Mühlebach
The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus...
July 14, 2017: Virus Genes
https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#15
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28705213/the-therapeutic-landscape-of-hiv-1-via-genome-editing
#16
REVIEW
Alexander Kwarteng, Samuel Terkper Ahuno, Godwin Kwakye-Nuako
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including several side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy, an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease, zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins (CRISPR-Cas9) are transforming the therapeutic landscape of HIV-1...
July 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28702025/cellular-and-molecular-defects-underlying-invasive-fungal-infections-revelations-from-endemic-mycoses
#17
REVIEW
Pamela P Lee, Yu-Lung Lau
The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28701402/increased-durable-b-cell-and-adcc-responses-associated-with-t-helper-responses-to-hiv-1-envelope-in-macaques-vaccinated-with-gp140-occluded-at-the-cd4-receptor-binding-site
#18
Willy M J M Bogers, Susan W Barnett, Herman Oostermeijer, Ivonne G Nieuwenhuis, Niels Beenhakker, Daniella Mortier, Petra Mooij, Gerrit Koopman, Edmund Remarque, Gregoire Martin, Rachel Pei-Jen Lai, Antu K Dey, Yide Sun, Brian Burke, Guido Ferrari, David Montefiori, Loic Martin, David Davis, Indresh Srivastava, Jonathan L Heeney
Strategies are needed to improve the immunogenicity of HIV-1 envelope (Env) antigens for more long lived, efficacious HIV-1 vaccine induced B-cell responses. HIV-1 Env gp140 (native or un-cleaved molecules) or gp120 monomeric proteins elicit relatively poor B-cell responses which are short-lived. We hypothesized that Env engagement of the CD4 receptor on T-helper cells may result in anergic effects on T-cell recruitment and consequently a lack of strong robust and durable B-memory responses. To test this hypothesis we occluded the CD4 binding site (CD4bs) of gp140 by stable cross-linking with a 3kD CD4 miniprotein mimetic serving to block ligation of gp140 on CD4+T-cells while preserving CD4 inducible (CDi) neutralizing and epitopes targeted by antibody dependent cellular cytotoxic (ADCC) effector responses...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701395/preferential-targeting-of-conserved-gag-regions-after-vaccination-with-a-heterologous-dna-prime-modified-vaccinia-ankara-mva-boost-hiv-1-vaccine-regimen
#19
Asli Bauer, Lilli Podola, Philipp Mann, Marco Missanga, Antelmo Haule, Lwitiho Sudi, Charlotta Nilsson, Bahati Kaluwa, Cornelia Lueer, Maria Mwakatima, Patricia J Munseri, Leonard Maboko, Merlin L Robb, Sodsai Tovanabutra, Gustavo Kijak, Mary Marovich, Sheena McCormack, Sarah Joseph, Eligius Lyamuya, Britta Wahren, Eric Sandström, Gunnel Biberfeld, Michael Hoelscher, Muhammad Bakari, Arne Kroidl, Christof Geldmacher
Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function and specificity of Gag-specific T cells induced by a DNA-prime Modified Vaccinia Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding for a subtype B and AB-recombinant Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701393/hiv-1-env-and-vpu-specific-antibody-dependent-cellular-cytotoxicity-responses-associated-with-elite-control-of-hiv
#20
Vijaya Madhavi, Bruce D Wines, Janaki Amin, Sean Emery, Ester Lopez, Anthony Kelleher, Rob J Center, P Mark Hogarth, Amy W Chung, Stephen J Kent, Ivan Stratov
Studying HIV-infected individuals who control HIV replication (elite controllers, ECs) enable exploration of effective anti-HIV immunity. HIV Env- and non-Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive HIV infection but the evidence is limited. We recruited 22 ECs and matched them with 44 viremic subjects. HIV Env- and Vpu-specific ADCC responses were studied in sera using a novel ELISA-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays and ADCC-mediated killing assays...
July 12, 2017: Journal of Virology
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