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https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#1
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636433/immunogenicity-of-ags-004-dendritic-cell-therapy-in-patients-treated-during-acute-hiv-infection
#2
Cynthia L Gay, Mark A DeBenedette, Irina Y Tcherepanova, Alicia Gamble, Whitney E Lewis, Anna B Cope, JoAnn D Kuruc, Kara S McGee, Mary F Kearney, John M Coffin, Nancie M Archin, Charles B Hicks, Joseph J Eron, Charles A Nicolette, David M Margolis
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4(+) T-cell infection (RCI) was measured by quantitative viral outgrowth assay...
June 21, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28633455/fetal-metabolic-stress-disrupts-immune-homeostasis-and-induces-pro-inflammatory-responses-in-hiv-1-and-cart-exposed-infants
#3
Johannes C Schoeman, Gontse P Moutloatse, Amy C Harms, Rob J Vreeken, Henriette J Scherpbier, Liesbeth Van Leeuwen, Taco W Kuijpers, Carools J Reinecke, Ruud Berger, Thomas Hankemeier, Madeleine J Bunders
Increased morbidity and fetal growth restriction are reported in uninfected children born to HIV-1-infected women treated with antiretroviral (ARV) therapy. Viruses and/or pharmacological interventions such as ARVs can induce metabolic stress skewing the cell's immune response and restricting (cell) growth. Novel metabolomic techniques provided the opportunity to investigate the impact of fetal HIV-1 and combination ARV therapy (cART)-exposure on the infants' immune-metabolome. Peroxidized lipids, generated by reactive oxygen species, were increased in cART/HIV-1-exposed infants, indicating altered mitochondrial functioning...
June 17, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28630473/impact-of-antigen-density-on-the-binding-mechanism-of-igg-antibodies
#4
Maya Hadzhieva, Anastas D Pashov, Srinivas Kaveri, Sébastien Lacroix-Desmazes, Hugo Mouquet, Jordan D Dimitrov
The density and distribution pattern of epitopes at the surface of pathogens have a profound impact on immune responses. Although multiple lines of evidence highlight the significance of antigen surface density for antibody binding, a quantitative description of its effect on recognition mechanisms is missing. Here, we analyzed binding kinetics and thermodynamics of six HIV-1 neutralizing antibodies as a function of the surface density of envelope glycoprotein gp120. Antibodies that recognize gp120 with low to moderate binding affinity displayed the most pronounced sensitivity to variation in antigen density, with qualitative and substantial quantitative changes in the energetics of the binding process as revealed by non-equilibrium and equilibrium thermodynamic analyses...
June 19, 2017: Scientific Reports
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
#5
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/28623917/the-dynamic-changes-of-interferon-lambdas-related-genes-and-proteins-in-jak-stat-pathway-in-both-acute-and-chronic-hiv-1-infected-patients
#6
Guoxian Zhao, Lifeng Liu, Bin Su, Tong Zhang, Peng Chen, Wei Li, Hao Wu
BACKGROUND: Host immune responses during acute HIV-1 infection can influence the viral setpoint, which is a predictor of disease progression. Interferon (IFN)-lambdas are newly classified type III interferons, which use JAK-STAT pathway. Currently, the dynamics of IFN-lambdas related genes and proteins expression in the signaling pathway have not been well elaborated, especially in acute HIV-1-infected patients. OBJECTIVES: To evaluate the dynamic changes of IFN-lambdas related genes and proteins in JAK/STAT pathway in acute HIV-1-infected patients, and analyze their correlation with CD4 T cell counts and HIV-1 viral loads...
June 17, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28622549/immunological-and-epidemiological-factors-affecting-candidiasis-in-hiv-patients-beginning-antiretroviral-therapy-in-an-asian-clinic
#7
Endah A T Wulandari, Henny Saraswati, Robiatul Adawiyah, Samsuridjal Djauzi, Retno Wahyuningsih, Patricia Price
OBJECTIVES: Oropharyngeal candidiasis (OPC) is common in HIV patients beginning antiretroviral therapy (ART). Here we address the response to ART, and the roles of poor oral hygiene and defects in local innate immunity with a focus on salivary β-defensins, as they are implicated in control of candidiasis but have not been investigated in this context. DESIGN: ART naïve HIV-infected adults (n=82) with <200 CD4(+) T-cells/mm(3) attending clinics at Cipto Mangunkusumo Hospital, Jakarta, were examined at the commencement of ART, and 73 were re-examined after 3 months...
June 3, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28620031/tspan7-effector-of-actin-nucleation-required-for-dendritic-cell-mediated-transfer-of-hiv-1-to-t-cells
#8
REVIEW
Mickaël M Ménager
Dendritic cells (DCs) have essential roles in early detection of pathogens and activation of both innate and adaptive immune responses. Whereas human DCs are resistant to productive HIV-1 replication, they have a unique ability to take up virus and transmit it efficiently to T lymphocytes. By doing that, HIV-1 may evade, at least in part, the first line of defense of the immune system, exploiting DCs instead to facilitate rapid infection of a large pool of immune cells. While performing an shRNA screen in human primary monocyte-derived DCs, to gain insights into this cell biological process, we discovered the role played by tetraspanin-7 (TSPAN7)...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28615205/intrasubtype-b-hiv-1-superinfection-correlates-with-delayed-neutralizing-antibody-response
#9
Gabriel A Wagner, Elise Landais, Gemma Caballero, Pham Phung, Sergei L Kosakovsky Pond, Pascal Poignard, Douglas D Richman, Susan J Little, Davey M Smith
Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures, and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART) naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615147/hiv-specific-b-cell-frequency-correlates-with-neutralization-breadth-in-patients-naturally-controlling-hiv-infection
#10
Angeline Rouers, Jéromine Klingler, Bin Su, Assia Samri, Géraldine Laumond, Sophie Even, Véronique Avettand-Fenoel, Clemence Richetta, Nicodème Paul, Faroudy Boufassa, Laurent Hocqueloux, Hugo Mouquet, Christine Rouzioux, Olivier Lambotte, Brigitte Autran, Stéphanie Graff-Dubois, Christiane Moog, Arnaud Moris
HIV-specific broadly neutralizing antibodies (bnAbs) have been isolated from patients with high viremia but also from HIV controllers that repress HIV-1 replication. In these elite controllers (ECs), multiple parameters contribute to viral suppression, including genetic factors and immune responses. Defining the immune correlates associated with the generation of bnAbs may help in designing efficient immunotherapies. In this study, in ECs either positive or negative for the HLA-B*57 protective allele, in treated HIV-infected and HIV-negative individuals, we characterized memory B cell compartments and HIV-specific memory B cells responses using flow cytometry and ELISPOT...
May 31, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28614691/a-trial-of-itraconazole-or-amphotericin-b-for-hiv-associated-talaromycosis
#11
RANDOMIZED CONTROLLED TRIAL
Thuy Le, Nguyen Van Kinh, Ngo T K Cuc, Nguyen L N Tung, Nguyen T Lam, Pham T T Thuy, Do D Cuong, Pham T H Phuc, Vu H Vinh, Doan T H Hanh, Vu Van Tam, Nguyen T Thanh, Tran P Thuy, Nguyen T Hang, Hoang B Long, Ho T Nhan, Heiman F L Wertheim, Laura Merson, Cecilia Shikuma, Jeremy N Day, Nguyen V V Chau, Jeremy Farrar, Guy Thwaites, Marcel Wolbers
BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking...
June 15, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28608842/talaromyces-marneffei-genomic-transcriptomic-proteomic-and-metabolomic-studies-reveal-mechanisms-for-environmental-adaptations-and-virulence
#12
REVIEW
Susanna K P Lau, Chi-Ching Tsang, Patrick C Y Woo
Talaromycesmarneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus...
June 13, 2017: Toxins
https://www.readbyqxmd.com/read/28607543/modulation-of-tryptophan-serotonin-pathway-by-probiotic-supplementation-in-human-immunodeficiency-virus-positive-patients-preliminary-results-of-a-new-study-approach
#13
Giuseppe Corano Scheri, Saeid Najafi Fard, Ivan Schietroma, Andrea Mastrangelo, Claudia Pinacchio, Noemi Giustini, Sara Serafino, Gabriella De Girolamo, Eugenio Nelson Cavallari, Maura Statzu, Luca Laghi, Annamaria Vullo, Giancarlo Ceccarelli, Vincenzo Vullo, Gabriella d'Ettorre
BACKGROUND: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1-infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy-treated patients and the subsistence of an interplay with inflammation...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28606402/clinical-histological-and-radiological-responses-to-methylprednisolone-in-hiv-associated-rod-myopathy
#14
André M S Silva, Rodrigo H Mendonça, Cristiane A M Moreno, Eduardo P Estephan, Paulo V P Helito, Mary S Carvalho, Edmar Zanoteli
Skeletal muscle involvement as a neurologic manifestation in individuals with HIV is rare, especially as rod myopathy. We describe a 41-year-old male with HIV infection who presented progressive proximal muscle weakness and limb-girdle atrophy. A muscle magnetic resonance image showed bilateral fatty infiltration and post-contrast enhancement in the arm and thigh muscles. The muscle biopsy revealed intracytoplasmic aggregates with appearance of nemaline rod bodies with Gomori trichrome staining and electron microscopy in most fibers...
May 12, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28605173/barriers-to-hiv-remission-research-in-low-and-middle-income-countries
#15
REVIEW
Theresa Rossouw, Joseph D Tucker, Gert U van Zyl, Kenly Sikwesi, Catherine Godfrey
INTRODUCTION: HIV eradication and remission research has largely taken place in high-income countries. In low- and middle-income countries (LMIC), there may be factors that have a substantial impact on the size of the latent HIV reservoir and the immunological response to infection. If a curative strategy is to be available to all HIV-infected individuals, these factors must be understood. METHODS: We use a scoping review to examine the literature on biological factors that may have an impact on HIV persistence in LMIC...
June 5, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28602843/combination-of-cell-penetrating-peptides-and-heterologous-dna-prime-protein-boost-strategy-enhances-immune-responses-against-hiv-1-nef-antigen-in-balb-c-mouse-model
#16
Somayeh Kadkhodayan, Behnaz Sadat Jafarzade, Seyed Mehdi Sadat, Fateme Motevalli, Elnaz Agi, Azam Bolhassani
To develop a strong HIV specific T-cell response, the HIV-1 Tat and Nef regulatory proteins have been known as attractive antigenic candidates in vaccine design. A peptide transduction domain of Tat (48-60 aa) could act to deliver other therapeutic molecules into different cells. In this line, several cell-penetrating peptides (CPPs) have been designed to transfer DNA, siRNA, polypeptides and proteins into cells through non-covalent approach such as CADY and PEP families. Some studies showed that the endogenous adjuvants including heat shock protein Gp96 could stimulate antigen-specific T cell immune responses...
June 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28599793/a-cross-reacting-material-crm197-conjugate-vaccine-induces-diphtheria-toxin-neutralizing-antibody-response-in-children-and-adolescents-infected-or-not-with-hiv
#17
Giselle P Silva, Rafaela S Santos, Wânia F Pereira-Manfro, Bianca Ferreira, Daniella M Barreto, Ana Cristina C Frota, Cristina B Hofer, Lucimar G Milagres
Anti-diphtheria antibody levels decrease with aging, and frequent booster vaccinations are required to maintain herd immunity. We analyzed the diphtheria toxin neutralizing antibody (DT-Nab) response induced by a conjugate vaccine (meningococcal C polysaccharide-CRM197) in HIV-vertically infected (HI) children and adolescents and healthy controls (HC) with matched age. We report the association of DT-Nab with the bactericidal antibodies to serogroup C meningococcus (MenC). Before vaccination, 21 HI patients (50%) had no protection against diphtheria (≤0...
June 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28597817/decreased-pro-inflammatory-immune-responses-during-recurrent-acute-hcv-infections-in-hiv-co-infected-patients
#18
Sebastiaan J Hullegie, Joop E A Arends, Zwier M A Groothuismink, Suzan D Pas, Bart J A Rijnders, Andre Boonstra, Mark A A Claassen
Patients in high-risk groups continue to transmit the hepatitis C virus (HCV) and frequently experience reinfections. Since little is known regarding the immune response to HCV during reinfection, we compared primary and consecutive acute HCV infections in patients with an HIV infection, and focused on the cytokine bridging innate to adaptive immunity. We observed that the serum levels of IL-12p40, MIP-1β, MIG and IP-10 increased during primary acute HCV infection, but not during subsequent secondary acute reinfections...
June 8, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28596770/a-phase-1-human-immunodeficiency-virus-vaccine-trial-for-cross-profiling-the-kinetics-of-serum-and-mucosal-antibody-responses-to-cn54gp140-modulated-by-two-homologous-prime-boost-vaccine-regimens
#19
Sven Kratochvil, Paul F McKay, Jakub T Kopycinski, Cynthia Bishop, Peter John Hayes, Luke Muir, Christopher L Pinder, Deniz Cizmeci, Deborah King, Yoann Aldon, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent, Kathrin Held, Christof Geldmacher, Len Dally, Nelson S Santos, Tom Cole, Jill Gilmour, Sarah Fidler, Robin J Shattock
A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28594894/micrornas-upregulated-during-hiv-infection-target-peroxisome-biogenesis-factors-implications-for-virus-biology-disease-mechanisms-and-neuropathology
#20
Zaikun Xu, Eugene L Asahchop, William G Branton, Benjamin B Gelman, Christopher Power, Tom C Hobman
HIV-associated neurocognitive disorders (HAND) represent a spectrum neurological syndrome that affects up to 25% of patients with HIV/AIDS. Multiple pathogenic mechanisms contribute to the development of HAND symptoms including chronic neuroinflammation and neurodegeneration. Among the factors linked to development of HAND is altered expression of host cell microRNAs (miRNAs) in brain. Here, we examined brain miRNA profiles among HIV/AIDS patients with and without HAND. Our analyses revealed differential expression of 17 miRNAs in brain tissue from HAND patients...
June 2017: PLoS Pathogens
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