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https://www.readbyqxmd.com/read/29451984/two-component-ferritin-nanoparticles-for-multimerization-of-diverse-trimeric-antigens
#1
Ivelin S Georgiev, Michael Gordon Joyce, Rita E Chen, Kwanyee Leung, Krisha McKee, Aliaksandr Druz, Joseph G Van Galen, Masaru Kanekiyo, Yaroslav Tsybovsky, Eun Sung Yang, Yongping Yang, Priyamvada Acharya, Marie Pancera, Paul V Thomas, Timothy Wanninger, Hadi Yassine, Ulrich Baxa, Nicole Doria-Rose, Cheng Cheng, Barney S Graham, John R Mascola, Peter D Kwong
Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (twenty-four monomers or eight trimers) of a single antigen. Here we design two-component ferritin variants that allow the attachment of two diverse antigens on a single particle in a defined ratio and geometric pattern...
February 16, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29451894/trade-off-between-synergy-and-efficacy-in-combinations-of-hiv-1-latency-reversing-agents
#2
Vipul Gupta, Narendra M Dixit
Eradicating HIV-1 infection is difficult because of the reservoir of latently infected cells that gets established soon after infection, remains hidden from antiretroviral drugs and host immune responses, and retains the capacity to reignite infection following the cessation of treatment. Drugs called latency-reversing agents (LRAs) are being developed to reactivate latently infected cells and render them susceptible to viral cytopathicity or immune killing. Whereas individual LRAs have failed to induce adequate reactivation, pairs of LRAs have been identified recently that act synergistically and hugely increase reactivation levels compared to individual LRAs...
February 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29449843/insights-into-the-structural-basis-of-antibody-affinity-maturation-from-next-generation-sequencing
#3
REVIEW
Arjun K Mishra, Roy A Mariuzza
Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism's own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29447279/regulatory-t-cells-in-retroviral-infections
#4
REVIEW
Kim J Hasenkrug, Claire A Chougnet, Ulf Dittmer
Tight regulation of immune responses is not only critical for preventing autoimmune diseases but also for preventing immunopathological damage during infections in which overactive immune responses may be more harmful for the host than the pathogen itself. Regulatory T cells (Tregs) play a critical role in this regulation, which was discovered using the Friend retrovirus (FV) mouse model. Subsequent FV studies revealed basic biological information about Tregs, including their suppressive activity on effector cells as well as the molecular mechanisms of virus-induced Treg expansion...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29447242/a-novel-ligand-on-astrocytes-interacts-with-natural-cytotoxicity-receptor-nkp44-regulating-immune-response-mediated-by-nk-cells
#5
Kelly E Bowen, Stephen O Mathew, Kathleen Borgmann, Anuja Ghorpade, Porunelloor A Mathew
NK cells play important role in immunity against pathogens and cancer. NK cell functions are regulated by inhibitory and activating receptors binding corresponding ligands on the surface of target cells. NK cells were shown to be recruited to the CNS following several pathological conditions. NK cells could impact CNS physiology by killing glial cells and by secreting IFN-γ. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS and reactive astrogliosis is a key feature in HIV-associated neurocognitive disorders...
2018: PloS One
https://www.readbyqxmd.com/read/29445452/exploiting-immune-cell-metabolic-machinery-for-functional-hiv-cure-and-the-prevention-of-inflammaging
#6
REVIEW
Clovis S Palmer, Riya Palchaudhuri, Hassan Albargy, Mohamed Abdel-Mohsen, Suzanne M Crowe
An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated...
2018: F1000Research
https://www.readbyqxmd.com/read/29444185/humoral-and-cell-mediated-immune-responses-after-a-booster-dose-of-hbv-vaccine-in-hiv-infected-children-adolescents-and-young-adults
#7
Vania Giacomet, Michela Masetti, Pilar Nannini, Federica Forlanini, Mario Clerici, Gian Vincenzo Zuccotti, Daria Trabattoni
OBJECTIVE: HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. DESIGN: 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. METHOD: All patients received a booster dose of HBV vaccine (HBVAXPRO 10 μg i...
2018: PloS One
https://www.readbyqxmd.com/read/29441069/interleukin-6-and-interferon-%C3%AE-signaling-via-jak1-stat-differentially-regulate-oncolytic-versus-cytoprotective-antiviral-states
#8
Oded Danziger, Tal Pupko, Eran Bacharach, Marcelo Ehrlich
Malignancy-induced alterations to cytokine signaling in tumor cells differentially regulate their interactions with the immune system and oncolytic viruses. The abundance of inflammatory cytokines in the tumor microenvironment suggests that such signaling plays key roles in tumor development and therapy efficacy. The JAK-STAT axis transduces signals of interleukin-6 (IL-6) and interferons (IFNs), mediates antiviral responses, and is frequently altered in prostate cancer (PCa) cells. However, how activation of JAK-STAT signaling with different cytokines regulates interactions between oncolytic viruses and PCa cells is not known...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29439476/virus-like-vaccines-against-hiv
#9
REVIEW
Anne-Marie C Andersson, Melanie Schwerdtfeger, Peter J Holst
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV...
February 11, 2018: Vaccines
https://www.readbyqxmd.com/read/29438131/improved-neurodevelopment-following-antiretroviral-therapy-in-hiv-infected-children
#10
Laurén A Gómez, Claudia S Crowell, Irene Njuguna, Lisa M Cranmer, Dalton Wamalwa, Daisy Chebet, Vincent Otieno, Elizabeth Maleche-Obimbo, Melissa Gladstone, Grace John-Stewart, Sarah Benki-Nugent
BACKGROUND: Late HIV diagnosis following severe co-morbidity remains common in resource limited settings. Neurodevelopmental recovery during antiretroviral therapy (ART) for late-diagnosed children is understudied. We determined 6-month neurodevelopmental trajectories in HIV-infected children initiating ART during hospitalization. METHODS: HIV-infected children initiated ART following HIV diagnosis during hospitalization in Kenya. The Malawi Developmental Assessment Tool (MDAT) was administered after clinical stabilization within 1-month and at 6-months post-ART initiation...
February 12, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29437277/identification-of-native-and-post-translationally-modified-hla-b-57-01-restricted-hiv-envelope-derived-epitopes-using-immunoproteomics
#11
Sri H Ramarathinam, Stephanie Gras, Sheilajen Alcantara, Amanda W S Yeung, Nicole A Mifsud, Secondo Sonza, Patricia T Illing, Elias N Glaros, Robert J Center, Shane Thomas, Stephen J Kent, Nicola Ternette, Damian F J Purcell, Jamie Rossjohn, Anthony W Purcell
The recognition of pathogen-derived peptides by T lymphocytes is the cornerstone of adaptive immunity, whereby intracellular antigens are degraded in the cytosol and short peptides assemble with class I human leukocyte antigen (HLA) molecules in the endoplasmic reticulum (ER). These peptide-HLA complexes egress to the cell surface and are scrutinized by cytotoxic CD8+ T-cells leading to the eradication of the infected cell. Here we identify naturally presented HLA-B*57:01 bound peptides derived from the envelope protein of the human immunodeficiency virus (HIVenv)...
February 13, 2018: Proteomics
https://www.readbyqxmd.com/read/29437254/crispr-cas9-knockout-of-usp18-enhances-type-i-ifn-responsiveness-and-restricts-hiv-1-infection-in-macrophages
#12
Jared P Taylor, Melanie N Cash, Katherine E Santostefano, Mahito Nakanishi, Naohiro Terada, Mark A Wallet
The IFN-stimulated gene ubiquitin-specific proteinase 18 (USP18) encodes a protein that negatively regulates T1 IFN signaling via stearic inhibition of JAK1 recruitment to the IFN-α receptor 2 subunit (IFNAR2). Here, we demonstrate that USP18 expression is induced by HIV-1 in a T1 IFN-dependent manner. Experimental depletion of USP18 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing results in a significant restriction of HIV-1 replication in an induced pluripotent stem cell (iPSC)-derived macrophage model...
February 13, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29432824/immune-response-to-antigen-adsorbed-to-aluminum-hydroxide-particles-effects-of-co-adsorption-of-alf-or-alfq-adjuvant-to-the-aluminum-antigen-complex
#13
Zoltan Beck, Oscar B Torres, Gary R Matyas, David E Lanar, Carl R Alving
Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA)...
February 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29429810/envelope-proteins-of-two-hiv-1-clades-induced-different-epitope-specific-antibody-response
#14
Tripti Shrivastava, Sweety Samal, Ashish K Tyagi, Sandeep Goswami, Naresh Kumar, Gabriel Ozorowski, Andrew B Ward, Bimal K Chakrabarti
Using HIV-1 envelope protein (Env)-based immunogens that closely mimic the conformation of functional HIV-1 Envs and represent the isolates prevalent in relevant geographical region is considered a rational approach towards developing HIV vaccine. We recently reported that like clade B Env, JRFL, membrane bound Indian clade C Env, 4-2.J41 is also efficiently cleaved and displays desirable antigenic properties for plasmid DNA immunization. Here, we evaluated the immune response in rabbit by injecting the animals with plasmid expressing membrane bound efficiently cleaved 4-2...
February 8, 2018: Vaccine
https://www.readbyqxmd.com/read/29427516/mechanisms-of-cd8-t-cell-mediated-suppression-of-hiv-siv-replication
#15
REVIEW
Julia Bergild McBrien, Nitasha A Kumar, Guido Silvestri
In this article, we summarize the role of CD8+ T cells during natural and ART-treated HIV and SIV infections, discuss the mechanisms responsible for their suppressive activity, and review the rationale for CD8+ T cell-based HIV cure strategies. Evidence suggests that CD8+ T cells are involved in the control of virus replication during HIV and SIV infections. During early HIV infection, the cytolytic activity of CD8+ T cells is responsible for control of viremia. However, it has been proposed that CD8+ T cells also use non-cytolytic mechanisms to control SIV infection...
February 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29427444/antibody-response-to-hepatitis-b-vaccine-in-hiv-exposed-infants-in-malawi-and-correlation-with-hbv-infection-acquisition
#16
Sandro Mancinelli, Maria Franca Pirillo, Giuseppe Liotta, Mauro Andreotti, Robert Mphwere, Roberta Amici, Maria Cristina Marazzi, Stefano Vella, Leonardo Palombi, Marina Giuliano
The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (> 10 mIU/ml) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (7 children were HBsAg+ at Month 24) occurred also in the presence of levels above 10 mIU/ml. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels > 10 mIU/ml may be required to confer protection in this context...
February 10, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29424780/insulin-like-growth-factor-1-inversely-relates-to-monocyte-macrophage-activation-markers-in-hiv
#17
Lindsay T Fourman, Natalia Czerwonka, Sofia D Shaikh, Takara L Stanley, Tricia H Burdo, Kenneth C Williams, Kathleen V Fitch, Janet Lo, Steven K Grinspoon
OBJECTIVE: Monocyte/macrophage activation is increased among people with HIV, and may contribute to the heightened risk of atherosclerosis and neurocognitive dysfunction in this population. Insulin-like growth factor 1 (IGF-1) has been shown to attenuate the innate immune response in animal models of atherosclerosis and inflammatory bowel disease. We investigated for the first time, relationships of circulating IGF-1 with monocyte/macrophage-specific indices among HIV-infected individuals and uninfected controls...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29424779/impact-of-aging-and-hiv-infection-on-serologic-response-to-seasonal-influenza-vaccination
#18
Suresh Pallikkuth, Lesley R De Armas, Rajendra Pahwa, Stefano Rinaldi, Varghese K George, Celeste M Sanchez, Li Pan, Gordon Dickinson, Allan Rodriguez, Margaret Fischl, Maria Alcaide, Savita Pahwa
OBJECTIVE: To determine influence of age and HIV infection on influenza vaccine responses. DESIGN: Evaluate serologic response to seasonal trivalent influenza vaccine (TIV) as the immunologic outcome in HIV-infected (HIV) and age-matched HIV negative (HIV) adults. METHODS: During 2013-2016, 151 virologically controlled HIV individuals on antiretroviral therapy and 164 HIV volunteers grouped by age as young (<40 years), middle aged (40-59 years) and old (≥60 years) were administered TIV and investigated for serum antibody response to vaccine antigens...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29424778/persistence-of-memory-b-cell-and-t-cell-responses-to-the-quadrivalent-hpv-vaccine-in-hiv-infected-children
#19
Adriana Weinberg, Sharon Huang, A B Moscicki, Afred Saah, Myron J Levin
OBJECTIVE: To determine the magnitude and persistence of quadrivalent human papillomavirus (HPV)16 and HPV18 B-cell and T-cell memory after three or four doses of quadrivalent HPV vaccine (QHPV) in HIV-infected children. METHODS: Seventy-four HIV-infected children immunized with four doses and 23 with three doses of QHPV had HPV16 and HPV18 IgG B-cell and IFNγ and IL2 T-cell ELISPOT performed at 2, 3.5 and 4-5 years after the last dose. RESULTS: HPV16 and HPV18 T-cell responses were similar in both treatment groups, with higher responses to HPV16 vs...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29421321/2017-international-meeting-of-the-global-virus-network
#20
REVIEW
Mike Catton, Glenda Gray, Diane Griffin, Hideki Hasegawa, Stephen Kent, Jason Mackenzie, Edward McSweegan, Natalia Mercer, Linfa Wang
The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 40 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. The 2017 meeting was held from September 25-27 in Melbourne, Australia, and was hosted by the Peter Doherty Institute for Infection and Immunity and the Institut Pasteur. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including the recent Zika epidemic, infections by human papillomavirus, influenza, HIV, hepatitis C, HTLV-1, and chikungunya viruses, and new and emerging viruses in the Australasia region...
February 5, 2018: Antiviral Research
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