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Broadly neutralizing antibody

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https://www.readbyqxmd.com/read/29023549/supraphysiologic-control-over-hiv-1-replication-mediated-by-cd8-t-cells-expressing-a-re-engineered-cd4-based-chimeric-antigen-receptor
#1
Rachel S Leibman, Max W Richardson, Christoph T Ellebrecht, Colby R Maldini, Joshua A Glover, Anthony J Secreto, Irina Kulikovskaya, Simon F Lacey, Sarah R Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A Dufendach, Michael C Holmes, Ronald G Collman, Aimee S Payne, James L Riley
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29021166/an-analysis-of-il-36-signature-genes-and-individuals-with-il1rl2-knockout-mutations-validates-il-36-as-a-psoriasis-therapeutic-target
#2
Satveer K Mahil, Marika Catapano, Paola Di Meglio, Nick Dand, Helena Ahlfors, Ian M Carr, Catherine H Smith, Richard C Trembath, Mark Peakman, John Wright, Francesca D Ciccarelli, Jonathan N Barker, Francesca Capon
Interleukin (IL)-36α, IL-36β, and IL-36γ are innate mediators of acute epithelial inflammation. We sought to demonstrate that these cytokines are also required for the pathogenesis of plaque psoriasis, a common and chronic skin disorder, caused by abnormal T helper 17 (TH17) cell activation. To investigate this possibility, we first defined the genes that are induced by IL-36 cytokines in primary human keratinocytes. This enabled us to demonstrate a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29020058/hiv-transmitted-founder-vaccines-elicit-autologous-tier-2-neutralizing-antibodies-for-the-cd4-binding-site
#3
Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson
Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30)...
2017: PloS One
https://www.readbyqxmd.com/read/29018261/alveolar-macrophages-are-critical-for-broadly-reactive-antibody-mediated-protection-against-influenza-a-virus-in-mice
#4
Wenqian He, Chi-Jene Chen, Caitlin E Mullarkey, Jennifer R Hamilton, Christine K Wong, Paul E Leon, Melissa B Uccellini, Veronika Chromikova, Carole Henry, Kevin W Hoffman, Jean K Lim, Patrick C Wilson, Matthew S Miller, Florian Krammer, Peter Palese, Gene S Tan
The aim of candidate universal influenza vaccines is to provide broad protection against influenza A and B viruses. Studies have demonstrated that broadly reactive antibodies require Fc-Fc gamma receptor interactions for optimal protection; however, the innate effector cells responsible for mediating this protection remain largely unknown. Here, we examine the roles of alveolar macrophages, natural killer cells, and neutrophils in antibody-mediated protection. We demonstrate that alveolar macrophages play a dominant role in conferring protection provided by both broadly neutralizing and non-neutralizing antibodies in mice...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018252/neutralization-of-zika-virus-by-germline-like-human-monoclonal-antibodies-targeting-cryptic-epitopes-on-envelope-domain-iii
#5
Yanling Wu, Shun Li, Lanying Du, Chunyu Wang, Peng Zou, Binbin Hong, Mengjiao Yuan, Xiaonan Ren, Wanbo Tai, Yu Kong, Chen Zhou, Lu Lu, Xiaohui Zhou, Shibo Jiang, Tianlei Ying
The Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, has emerged as a global public health concern. Pre-existing cross-reactive antibodies against other flaviviruses could modulate immune responses to ZIKV infection by antibody-dependent enhancement, highlighting the importance of understanding the immunogenicity of the ZIKV envelope protein. In this study, we identified a panel of human monoclonal antibodies (mAbs) that target domain III (DIII) of the ZIKV envelope protein from a very large phage-display naive antibody library...
October 11, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28994411/x-ray-and-em-structures-of-a-natively-glycosylated-hiv-1-envelope-trimer
#6
Harry B Gristick, Haoqing Wang, Pamela J Bjorkman
The structural and biochemical characterization of broadly neutralizing anti-HIV-1 antibodies (bNAbs) has been essential in guiding the design of potential vaccines to prevent infection by HIV-1. While these studies have revealed critical mechanisms by which bNAbs recognize and/or accommodate N-glycans on the trimeric envelope glycoprotein (Env), they have been limited to the visualization of high-mannose glycan forms only, since heterogeneity introduced from the presence of complex glycans makes it difficult to obtain high-resolution structures...
October 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28994384/-follicular-helper-t-cells-and-hiv-united-for-better-and-worse
#7
Angeline Rouers, Raphaël Jeger-Madiot, Arnaud Moris, Stéphanie Graff-Dubois
Follicular helper T cells (Tfh) have been discovered in lymph nodes and, since then, are the focus of very intensive research to understand their origin, differentiation and functions. Tfh interact with B cells in the secondary lymphoid organs leading to B cell differentiation and maturation. Tfh are particularly studied in pathological contexts such as autoimmune diseases and infection by the human immunodeficiency virus (HIV). In the context of HIV infection, broadly neutralizing antibodies have been identified in a few patients...
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28993601/potency-of-an-inactivated-influenza-vaccine-prepared-from-a-duck-hokkaido-162-2013-h2n1-against-a-challenge-with-a-swine-missouri-2124514-2006-h2n3-in-mice
#8
Mizuho Suzuki, Masatoshi Okamatsu, Takahiro Hiono, Keita Matsuno, Yoshihiro Sakoda
H2N2 influenza virus caused a pandemic starting in 1957 but has not been detected in humans since 1968. Thus, most people are immunologically naive to viruses of the H2 subtype. In contrast, H2 influenza viruses are continually isolated from wild birds, and H2N3 viruses were isolated from pigs in 2006. H2 influenza viruses could cause a pandemic if re-introduced into humans. In the present study, a vaccine against H2 influenza was prepared as an effective control measure against a future human pandemic. A/duck/Hokkaido/162/2013 (H2N1), which showed broad antigenic cross-reactivity, was selected from the candidate H2 influenza viruses recently isolated from wild birds in Asian countries...
October 7, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28993460/evaluation-of-a-plasmodium-specific-carrier-protein-to-enhance-production-of-recombinant-pfs25-a-leading-transmission-blocking-vaccine-candidate
#9
Elizabeth M Parzych, Kazutoyo Miura, Aarti Ramanathan, Carole A Long, James M Burns
Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multi-antigen vaccine. Attempting to resolve these issues, we focused on the use of the highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that genetic fusion of the C-terminal 19 kDa fragment of merozoite surface protein 1 (MSP119) to PfMSP8 facilitated antigen production, folding and induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the rPfMSP8 carrier by introduction of two cysteine to serine substitutions (CΔS) to improve the yield of monomeric product...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28983040/broadly-neutralizing-antibodies-to-prevent-hiv-1
#10
Myron S Cohen, Lawrence Corey
No abstract text is available yet for this article.
October 6, 2017: Science
https://www.readbyqxmd.com/read/28982260/immunization-with-clinical-hiv-1-env-proteins-induces-broad-antibody-dependent-cellular-cytotoxicity-adcc-mediating-antibodies-in-a-rabbit-vaccination-model
#11
Ingrid Karlsson, Marie Borggren, Sanne Skov Jensen, Leo Heyndrickx, Guillaume Stewart-Jones, Gabriella Scarlatti, Anders Fomsgaard
The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, e.g., antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone and DNA prime with protein boost...
October 6, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28978939/non-neutralizing-antibodies-targeting-the-v1v2-domain-of-hiv-exhibit-strong-antibody-dependent-cell-mediated-cytotoxic-activity
#12
Luzia M Mayr, Thomas Decoville, Sylvie Schmidt, Géraldine Laumond, Jéromine Klingler, Camille Ducloy, Seiamak Bahram, Susan Zolla-Pazner, Christiane Moog
The development of an effective vaccine against HIV-1 has proven to be challenging. Broadly neutralizing antibodies (bNAbs), whilst exhibiting neutralization breadth and potency, are elicited only in a small subset of infected individuals and have yet to be induced by vaccination. Case-control studies of RV144 identified an inverse correlation of HIV-1 infection risk with antibodies (Abs) to the V1V2 region of gp120 with high antibody-dependent cellular cytotoxicity (ADCC) activity. The neutralizing activity of Abs was not found to contribute to this protective outcome...
October 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978711/functional-stability-of-hiv-1-envelope-trimer-affects-accessibility-to-broadly-neutralizing-antibodies-at-its-apex
#13
Syna Kuriakose Gift, Daniel P Leaman, Lei Zhang, Arthur S Kim, Michael B Zwick
The trimeric envelope glycoprotein spike (Env) of HIV-1 is the target of vaccine development to elicit broadly neutralizing antibodies (bnAbs). Env trimer instability and heterogeneity in principle make subunit interfaces inconsistent targets for the immune response. Here, we investigate how functional stability of Env relates to neutralization sensitivity to V2 bnAbs and V3 crown antibodies that engage subunit interfaces upon binding to unliganded Env. Env heterogeneity was inferred when antibodies neutralized a mutant Env with a plateau of less than 100% percentage neutralization...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28978710/cobra-ha-elicits-hemagglutination-inhibition-antibodies-against-a-panel-of-h3n2-influenza-virus-co-circulating-variants
#14
Terianne M Wong, James D Allen, Anne-Gaelle Bebin-Blackwell, Donald M Carter, Timothy Alefantis, Joshua DiNapoli, Harold Kleanthous, Ted M Ross
Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, 1-2 influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype specific influenza vaccines, a methodology called computationally optimized broadly reactive antigens (COBRA) was used to design novel hemagglutinin (HA) vaccine immunogens. COBRA technology was effectively used to design HA immunogens that elicited antibodies that neutralized H5N1 and H1N1 isolates...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28978475/elicitation-of-neutralizing-antibodies-targeting-the-v2-apex-of-the-hiv-envelope-trimer-in-a-wild-type-animal-model
#15
James E Voss, Raiees Andrabi, Laura E McCoy, Natalia de Val, Roberta P Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N Khan, Fernando Garces, Laura K Pritchard, Richard T Wyatt, Andrew B Ward, Max Crispin, Ian A Wilson, Dennis R Burton
Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28972148/time-course-negative-stain-electron-microscopy-based-analysis-for-investigating-protein-protein-interactions-at-the-single-molecule-level
#16
Bartek Nogal, Charles A Bowman, Andrew B Ward
Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate timescale...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28971971/potent-peptidic-fusion-inhibitors-of-influenza-virus
#17
Rameshwar U Kadam, Jarek Juraszek, Boerries Brandenburg, Christophe Buyck, Wim B G Schepens, Bart Kesteleyn, Bart Stoops, Rob Vreeken, Jan Vermond, Wouter Goutier, Chan Tang, Ronald Vogels, Robert H E Friesen, Jaap Goudsmit, Maria J P van Dongen, Ian A Wilson
Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential new pandemics, emerging viruses, and constantly mutating circulating strains. We report here on design and structural characterization of potent peptidic inhibitors against influenza hemagglutinin (HA). The peptide design was based on complementarity determining region (CDR) loops of anti-HA human broadly neutralizing antibodies, FI6v3 and CR9114. The optimized peptides exhibit nanomolar affinity and neutralization against group 1 influenza A viruses including the 2009 H1N1 pandemic and avian H5N1 strains...
September 28, 2017: Science
https://www.readbyqxmd.com/read/28970835/immunologic-insights-on-the-membrane-proximal-external-region-a-major-human-immunodeficiency-virus-type-1-vaccine-target
#18
REVIEW
Luis M Molinos-Albert, Bonaventura Clotet, Julià Blanco, Jorge Carrillo
Broadly neutralizing antibodies (bNAbs) targeting conserved regions within the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein (Env) can be generated by the human immune system and their elicitation by vaccination will be a key point to protect against the wide range of viral diversity. The membrane proximal external region (MPER) is a highly conserved region within the Env gp41 subunit, plays a major role in membrane fusion and is targeted by naturally induced bNAbs. Therefore, the MPER is considered as an attractive vaccine target...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28970483/epitope-associated-and-specificity-focused-features-of-ev71-neutralizing-antibody-repertoires-from-plasmablasts-of-infected-children
#19
Kuan-Ying Arthur Huang, Mei-Feng Chen, Yhu-Chering Huang, Shin-Ru Shih, Cheng-Hsun Chiu, Jainn-Jim Lin, Jen-Ren Wang, Kuo-Chien Tsao, Tzou-Yien Lin
Protective antibody levels are critical for protection from severe enterovirus 71 infection. However, little is known about the specificities and functional properties of the enterovirus 71-specific antibodies induced by natural infection in humans. Here we characterize 191 plasmablast-derived monoclonal antibodies from three enterovirus 71-infected children, each of whom shows a distinct serological response. Of the 84 enterovirus 71-specific antibodies, neutralizing antibodies that target the rims and floor of the capsid canyon exhibit broad and potent activities at the nanogram level against viruses isolated in 1998-2016...
October 2, 2017: Nature Communications
https://www.readbyqxmd.com/read/28968993/human-papillomavirus-16l1-58l2-chimeric-virus-like-particles-elicit-durable-neutralizing-antibody-responses-against-a-broad-spectrum-of-human-papillomavirus-types
#20
Xue Chen, Hongyang Liu, Zhirong Wang, Shuo Wang, Ting Zhang, Meili Hu, Liang Qiao, Xuemei Xu
The neutralizing antibodies elicited by human papillomavirus (HPV) major capsid protein L1 virus-like particle (VLP)-based vaccines are largely type-specific. An HPV vaccine inducing cross-neutralizing antibodies broadly will be cost-effective and of great value. To this end, we constructed HPV16L1-58L2 chimeric VLP (cVLP) by displaying HPV58 L2 aa.16-37 on the DE surface region of HPV16 L1. We found that vaccination with the HPV16L1-58L2 cVLP formulated with alum plus monophosphoryl lipid A (Alum-MPL) adjuvant elicited robust neutralizing antibodies in both mice and rabbits against all tested HPV types including HPV16/31/33/35/52/58 (genus α9), HPV18/39/45/59/68 (genus α7), HPV6/11 (genus α10), HPV2/27/57 (genus α4), and HPV5 (genus β1)...
September 8, 2017: Oncotarget
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