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Broadly neutralizing antibodies

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https://www.readbyqxmd.com/read/28332627/cross-neutralizing-anti-hiv-1-human-single-chain-variable-fragments-scfvs-against-cd4-binding-site-and-n332-glycan-identified-from-a-recombinant-phage-library
#1
Lubina Khan, Rajesh Kumar, Ramachandran Thiruvengadam, Hilal Ahmad Parray, Muzamil Ashraf Makhdoomi, Sanjeev Kumar, Heena Aggarwal, Madhav Mohata, Abdul Wahid Hussain, Raksha Das, Raghavan Varadarajan, Jayanta Bhattacharya, Madhu Vajpayee, K G Murugavel, Suniti Solomon, Subrata Sinha, Kalpana Luthra
More than 50% of HIV-1 infection globally is caused by subtype_C viruses. Majority of the broadly neutralizing antibodies (bnAbs) targeting HIV-1 have been isolated from non-subtype_C infected donors. Mapping the epitope specificities of bnAbs provides useful information for vaccine design. Recombinant antibody technology enables generation of a large repertoire of monoclonals with diverse specificities. We constructed a phage recombinant single chain variable fragment (scFv) library with a diversity of 7.8 × 10(8) clones, using a novel strategy of pooling peripheral blood mononuclear cells (PBMCs) of six select HIV-1 chronically infected Indian donors whose plasma antibodies exhibited potent cross neutralization efficiency...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28331095/divergent-requirement-of-fc-fc%C3%AE-r-interactions-for-in-vivo-protection-against-influenza-viruses-by-two-pan-h5-hemagglutinin-antibodies
#2
Shuangshuang Wang, Huanhuan Ren, Wenbo Jiang, Honglin Chen, Hongxing Hu, Zhiwei Chen, Paul Zhou
Recent studies have shown that Fc-FcγR interactions are required for in vivo protection against influenza viruses by broadly reactive anti-HA stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS, and whether the requirement is virus strain-specific or epitope-specific...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28331080/evaluation-of-the-immune-responses-to-and-cross-protective-efficacy-of-eurasian-h7-avian-influenza-viruses
#3
Hyeok-Il Kwon, Young-Il Kim, Su-Jin Park, Min-Suk Song, Eun-Ha Kim, Se Mi Kim, Young-Jae Si, In-Won Lee, Byung-Min Song, Youn-Jeong Lee, Seok Joong Yun, Wun-Jae Kim, Young Ki Choi
Due to increasing concerns of human infection by various H7 viruses, including recent H7N9 viruses, we evaluated the genetic relationships and the cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analysis revealed that recent Eurasian H7 viruses can be separated into two different lineages with relatively high amino acid identity within groups (94.8 to 98.8%), and low amino acid identity (90.3 to 92.6 %) between the groups. In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive HI titers were approximately fourfold lower against heterologous group viruses compared to homologous group viruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28315836/a-phylogenetic-codon-substitution-model-for-antibody-lineages
#4
Kenneth B Hoehn, Gerton Lunter, Oliver G Pybus
Phylogenetic methods have shown promise in understanding the development of broadly neutralizing antibody lineages (bNAbs). However, the mutational process that generates these lineages -- somatic hypermutation -- is biased by hotspot motifs, which violates important assumptions in most phylogenetic substitution models. Here, we develop a modified GY94-type substitution model that partially accounts for this context-dependency while preserving independence of sites during calculation. This model shows a substantially better fit to three well-characterized bNAb lineages than the standard GY94 model...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28300601/functional-contacts-between-mper-and-the-anti-hiv-1-broadly-neutralizing-antibody-4e10-extend-into-the-core-of-the-membrane
#5
Edurne Rujas, Sara Insausti, Miguel García-Porras, Rubén Sánchez-Eugenia, Kouhei Tsumoto, José L Nieva, Jose M M Caaveiro
The exceptional breadth of broadly neutralizing antibodies (bNAbs) against the membrane-proximal external region (MPER) of the transmembrane protein gp41 makes this class of antibodies an ideal model to design HIV vaccines. From a practical point of view, however, the preparation of vaccines eliciting bNAbs is still a major roadblock that limits their clinical application. Fresh mechanistic insights are necessary to develop more effective strategies. In particular, the function of the unusually long complementary determining region three of the heavy chain (CDRH3) of 4E10, an anti-MPER bNAb, is an open question that fascinates researchers in the field...
March 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28298421/mimicry-of-an-hiv-broadly-neutralizing-antibody-epitope-with-a-synthetic-glycopeptide
#6
S Munir Alam, Baptiste Aussedat, Yusuf Vohra, R Ryan Meyerhoff, Evan M Cale, William E Walkowicz, Nathan A Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M Gordon Joyce, Marie Pancera, Aliaksandr Druz, Ivelin S Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven G Reed, Mark Louder, Robert T Bailer, Lynn Morris, Salim S Abdool-Karim, Myron Cohen, Hua-Xin Liao, David C Montefiori, Peter K Park, Alberto Fernández-Tejada, Kevin Wiehe, Sampa Santra, Thomas B Kepler, Kevin O Saunders, Joseph Sodroski, Peter D Kwong, John R Mascola, Mattia Bonsignori, M Anthony Moody, Samuel Danishefsky, Barton F Haynes
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28298420/staged-induction-of-hiv-1-glycan-dependent-broadly-neutralizing-antibodies
#7
Mattia Bonsignori, Edward F Kreider, Daniela Fera, R Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S Munir Alam, Baptiste Aussedat, William E Walkowicz, Kwan-Ki Hwang, Kevin O Saunders, Ruijun Zhang, Morgan A Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K Louder, Krisha McKee, Robert T Bailer, Brendan W Pier, Claudia A Jette, Garnett Kelsoe, Wilton B Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S Cohen, Peter T Hraber, David C Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B Kepler, M Anthony Moody, Feng Gao, Samuel J Danishefsky, John R Mascola, George M Shaw, Beatrice H Hahn, Stephen C Harrison, Bette T Korber, Barton F Haynes
A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28289286/early-antibody-therapy-can-induce-long-lasting-immunity-to-shiv
#8
Yoshiaki Nishimura, Rajeev Gautam, Tae-Wook Chun, Reza Sadjadpour, Kathryn E Foulds, Masashi Shingai, Florian Klein, Anna Gazumyan, Jovana Golijanin, Mitzi Donaldson, Olivia K Donau, Ronald J Plishka, Alicia Buckler-White, Michael S Seaman, Jeffrey D Lifson, Richard A Koup, Anthony S Fauci, Michel C Nussenzweig, Malcolm A Martin
Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans. In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant long-term infection control...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28285152/development-of-a-vaccine-against-cytomegalovirus-infection-and-disease
#9
REVIEW
Kate Luisi, Mayuri Sharma, Dong Yu
Human cytomegalovirus causes disabling congenital disease in neonates and severe complications in immunocompromised individuals, making it a high priority for vaccine development. A prophylactic vaccine needs to outperform natural immunity and a therapeutic vaccine needs to elicit rapid protective antiviral responses. This review highlights the three major approaches undertaken by vaccine developers-virus-derived, protein subunit, and gene-based approaches. Each approach offers a unique promise for a successful vaccine by eliciting either a broad immune response or inducing neutralizing antibody responses order(s) of magnitudes greater than natural immunity...
March 9, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28284876/dual-immunity-concomitantly-suppresses-hiv-1-progression
#10
Huma Qureshi, Jayanta Bhattacharya
Broadly neutralizing antibodies (bnAbs) elicited in HIV-1(+) elite neutralizers typically are unable to reduce viremia in the same individuals from whom they are isolated. A recent study reports the development of bnAbs in an elite controller that, along with the help of T cells, were associated with restricting HIV-1 progression.
March 8, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28284234/humoral-immune-system-targets-clonotypic-antibody-associated-hepatitis-c-virus
#11
Amruta S Naik, Brendan A Palmer, Orla Crosbie, Elizabeth Kenny-Walsh, Liam J Fanning
Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430). Furthermore, we generated HCV pseudoparticles (HCVpp) derived from AAV sequences to assess their infectivity...
February 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28283570/stabilization-of-a-soluble-native-like-trimeric-form-of-an-efficiently-cleaved-indian-hiv-1-clade-c-envelope-glycoprotein
#12
Shubbir Ahmed, Tripti Shrivastava, Naresh Kumar, Gabriel Ozorowski, Andrew B Ward, Bimal K Chakrabarti
Designing an effective HIV-1 envelope glycoprotein (Env) immunogen for elicitation of broadly neutralizing antibodies (bNAbs) is a challenging task owing to the high sequence diversity, heavy glycosylation and inherent meta-stability of Env. Based on the antigenic profile of recently isolated bNAbs, the rational approach to immunogen design is to make a stable version of the Env trimer, which mimics the native trimeric Env present on the viral surface. The SOSIP.664 form of a clade A Env, BG505, yields a homogeneous and well-ordered pre-fusion trimeric form, which maintains structural integrity and desired antigenicity...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28281871/progress-in-hiv-vaccine-development
#13
Denise C Hsu, Robert J O'Connell
An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials...
March 10, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28275193/structure-based-design-of-a-soluble-prefusion-closed-hiv-1-env-trimer-with-reduced-cd4-affinity-and-improved-immunogenicity
#14
Gwo-Yu Chuang, Hui Geng, Marie Pancera, Kai Xu, Cheng Cheng, Priyamvada Acharya, Michael Chambers, Aliaksandr Druz, Yaroslav Tsybovsky, Timothy G Wanninger, Yongping Yang, Nicole A Doria-Rose, Ivelin S Georgiev, Jason Gorman, M Gordon Joyce, Sijy O'Dell, Tongqing Zhou, Adrian B McDermott, John R Mascola, Peter D Kwong
The HIV-1-envelope (Env) trimer is a target for vaccine design as well as a conformational machine that facilitates virus entry by transitioning between prefusion-closed, CD4-bound, and co-receptor-bound conformations before rearranging into a postfusion state. Vaccine designers have sought to restrict the conformation of the HIV-1-Env trimer to its prefusion-closed state, as this state is recognized by most broadly neutralizing -but not by non-neutralizing- antibodies. We previously identified a disulfide bond, I201C-A433C (DS), which stabilizes Env in the vaccine-desired prefusion-closed state...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275185/broadly-reactive-anti-rsv-g-antibodies-from-exposed-individuals-effectively-inhibit-infection-of-primary-airway-epithelial-cells
#15
B Cortjens, E Yasuda, X Yu, K Wagner, Y B Claassen, A Q Bakker, J B M van Woensel, T Beaumont
Respiratory syncytial virus (RSV) causes severe respiratory disease in young children. Antibodies specific for the RSV prefusion F protein have guided RSV vaccine research and in human serum these antibodies attribute to >90% of the neutralization response, however detailed insight in the composition of the human B cell repertoire against RSV is still largely unknown. In order to study the B cell repertoire of 3 healthy donors for specificity against RSV, CD27(+) memory B cells were isolated and immortalized using BCL6 and Bcl-xL...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28272983/dynamics-of-8g12-competitive-antibody-in-prime-boost-vaccination-of-hepatitis-e-vaccine
#16
Xing Wu, Pan Chen, Huijuan Lin, Yao Su, Xiaotian Hao, Fengyu Cao, Li Li, Fengcai Zhu, Zhenglun Liang
Hepatitis E virus still poses a great threat to public health worldwide. To date, Hecolin® is the only licensed HEV vaccine in China. Total anti-HEV antibody has been used to reflect vaccine induced immune response in clinical trials for the lack of robust HEV neutralizing antibody detection methods. In this study, we applied a broad neutralizing mouse monoclonal antibody 8G12 to develop a competitive ELSIA assay and quantified 8G12 competitive antibody (8G12-like antibody) in serum samples. The presence of 8G12-like antibody was detected both from participants from HEV vaccine clinical trial and mice immunized with HEV vaccine...
March 8, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28257303/effective-hiv-vaccine-narrow-path-to-broadly-neutralizing-antibodies
#17
Ralf Wagner
No abstract text is available yet for this article.
March 10, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28257302/progress-in-hiv-1-antibody-research-using-humanized-mice
#18
Henning Gruell, Florian Klein
PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing antibodies provide new opportunities to successfully prevent, treat, and potentially cure HIV-1 infection. To test their activity in vivo, humanized mice have been shown to be a powerful model and were used to investigate antibody-mediated prevention and therapy approaches. In this review, we will summarize recent findings in humanized mice that have informed on the potential use of broadly neutralizing antibodies targeting HIV-1 in humans...
March 2, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28257301/adjuvants-tailoring-humoral-immune-responses
#19
M Juliana McElrath
PURPOSE OF REVIEW: The development and availability of new-generation adjuvants beyond aluminum and emulsion formulations, together with a deeper understanding of the mechanistic role of adjuvant formulations in stimulating innate immunity and offer opportunities to improve candidate vaccine designs intended to protect against HIV-1 acquisition. RECENT FINDINGS: Currently, major efforts in vaccine development focus on improving prime-boost vaccine regimens to enhance efficacy beyond 31% observed in the RV144 phase 3 study and to develop a pathway to induce broadly reactive HIV neutralizing antibodies...
March 2, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28257300/guiding-the-long-way-to-broad-hiv-neutralization
#20
David Peterhoff, Ralf Wagner
PURPOSE OF REVIEW: It has been demonstrated that extensive virus diversification and antibody coevolution are necessary to give rise to broadly neutralizing antibodies targeting the envelope protein of HIV-1. Here, we discuss recent progress of vaccine design approaches aiming on strategies to initiate and guide B-cell development toward this outcome, as well as their evaluation in mouse models engineered to express human antibodies. RECENT FINDINGS: Several specially tailored transgenic mouse strains have been developed to test the concept of engaging and guiding B-cell development by sequential immunizations...
March 2, 2017: Current Opinion in HIV and AIDS
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