keyword
MENU ▼
Read by QxMD icon Read
search

Broadly neutralizing antibodies

keyword
https://www.readbyqxmd.com/read/28534525/covalently-linked-dengue-virus-envelope-glycoprotein-dimers-reduce-exposure-of-the-immunodominant-fusion-loop-epitope
#1
Alexander Rouvinski, Wanwisa Dejnirattisai, Pablo Guardado-Calvo, Marie-Christine Vaney, Arvind Sharma, Stéphane Duquerroy, Piyada Supasa, Wiyada Wongwiwat, Ahmed Haouz, Giovanna Barba-Spaeth, Juthathip Mongkolsapaya, Félix A Rey, Gavin R Screaton
A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28528961/gp5-of-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-as-a-target-for-homologous-and-broadly-neutralizing-antibodies
#2
REVIEW
Luca N Popescu, Benjamin R Trible, Nanhua Chen, Raymond R R Rowland
Virus neutralization (VN) responses range from narrowly focused antibodies with only homologous neutralizing activity against the virus used for infection, to antibodies that can neutralize both Type 1 and Type 2 viruses, referred to as broadly neutralizing antibody (bnAb). Even though neutralizing epitopes are likely distributed among several structural glycoproteins, this paper focuses on the ectodomain region of GP5 as a model system for investigating the role for neutralizing and non-neutralizing antibodies in protection and disease...
April 29, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28527859/tackling-influenza-with-broadly-neutralizing-antibodies
#3
REVIEW
Davide Corti, Elisabetta Cameroni, Barbara Guarino, Nicole L Kallewaard, Qing Zhu, Antonio Lanzavecchia
Monoclonal antibodies have revolutionized the treatment of several human diseases, including cancer, autoimmunity and inflammatory conditions and represent a new frontier for the treatment of infectious diseases. In the last decade, new methods have allowed the efficient interrogation of the human antibody repertoire from influenza immune individuals and the isolation of several monoclonal antibodies capable of dealing with the high variability of influenza viruses. Here, we will provide a comprehensive overview of the specificity, antiviral and immunological mechanisms of action and development into the clinic of broadly reactive monoclonal antibodies against influenza A and B viruses...
May 18, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#4
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#5
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28515302/transposon-mutagenesis-of-the-zika-virus-genome-highlights-regions-essential-for-rna-replication-and-restricted-for-immune-evasion
#6
Benjamin O Fulton, David Sachs, Megan C Schwarz, Peter Palese, Matthew J Evans
The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the MR766 ZIKV genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514679/size-doesn-t-matter-shorter-antibody-loops-can-infiltrate-hiv-s-env-apex-defenses
#7
Jinal N Bhiman, Penny L Moore
An HIV vaccine that elicits broadly neutralizing antibodies, which often have unusual structural features, has not yet been developed. In Immunity this month, Cale et al., 2017 describe how a new mode of binding allows a conventional antibody to infiltrate HIV's armor.
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28514282/recent-progress-in-anti-hiv-broadly-neutralizing-antibody-research
#8
Stacey C Tobin
No abstract text is available yet for this article.
May 16, 2017: AIDS
https://www.readbyqxmd.com/read/28509878/antigenic-and-biological-characterization-of-orf2-6-variants-at-early-times-following-prrsv-infection
#9
Alyssa B Evans, Hyelee Loyd, Jenelle R Dunkelberger, Sarah van Tol, Marcus J Bolton, Karin S Dorman, Jack C M Dekkers, Susan Carpenter
Genetic diversity of porcine reproductive and respiratory syndrome virus (PRRSV) challenges efforts to develop effective and broadly acting vaccines. Although genetic variation in PRRSV has been extensively documented, the effects of this variation on virus phenotype are less well understood. In the present study, PRRSV open reading frame (ORF)2-6 variants predominant during the first six weeks following experimental infection were characterized for antigenic and replication phenotype. There was limited genetic variation during these early times after infection; however, distinct ORF2-6 haplotypes that differed from the NVSL97-7895 inoculum were identified in each of the five pigs examined...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28505154/dissecting-the-human-serum-antibody-response-to-secondary-dengue-virus-infections
#10
Bhumi Patel, Patti Longo, Michael J Miley, Magelda Montoya, Eva Harris, Aravinda M de Silva
Dengue viruses (DENVs) are mosquito-borne flaviviruses and the causative agents of dengue fever and dengue hemorrhagic fever. As there are four serotypes of DENV (DENV1-4), people can be infected multiple times, each time with a new serotype. Primary infections stimulate antibodies that mainly neutralize the serotype of infection (type-specific), whereas secondary infections stimulate responses that cross-neutralize 2 or more serotypes. Previous studies have demonstrated that neutralizing antibodies induced by primary infections recognize tertiary and quaternary structure epitopes on the viral envelope (E) protein that are unique to each serotype...
May 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28504265/in-vitro-evolution-of-an-influenza-broadly-neutralizing-antibody-is-modulated-by-hemagglutinin-receptor-specificity
#11
Nicholas C Wu, Geramie Grande, Hannah L Turner, Andrew B Ward, Jia Xie, Richard A Lerner, Ian A Wilson
The relatively recent discovery and characterization of human broadly neutralizing antibodies (bnAbs) against influenza virus provide valuable insights into antiviral and vaccine development. However, the factors that influence the evolution of high-affinity bnAbs remain elusive. We therefore explore the functional sequence space of bnAb C05, which targets the receptor-binding site (RBS) of influenza haemagglutinin (HA) via a long CDR H3. We combine saturation mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to H1 and H3 HAs...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28490598/development-of-clade-specific-and-broadly-reactive-live-attenuated-influenza-virus-vaccines-against-rapidly-evolving-h5-subtype-viruses
#12
Kobporn Boonnak, Yumiko Matsuoka, Weijia Wang, Amorsolo L Suguitan, Zhongying Chen, Myeisha Paskel, Mariana Baz, Ian Moore, Hong Jin, Kanta Subbarao
We have developed pandemic live attenuated influenza vaccines (pLAIV) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt that prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs: first to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade 2.2.1.1 virus A/Egypt/N03434/2009 (Egy/09) (H5N1) with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca The second approach was to select a low pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses and contained a novel NA subtype for humans...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28489039/third-generation-antivenomics-pushing-the-limits-of-the-in-vitro-preclinical-assessment-of-antivenoms
#13
Davinia Pla, Yania Rodríguez, Juan J Calvete
Second generation antivenomics is a translational venomics approach designed to complement in vivo preclinical neutralization assays. It provides qualitative and quantitative information on the set of homologous and heterologous venom proteins presenting antivenom-recognized epitopes and those exhibiting impaired immunoreactivity. In a situation of worrying antivenom shortage in many tropical and sub-tropical regions with high snakebite mortality and morbidity rates, such knowledge has the potential to facilitate the optimal deployment of currently existing antivenoms and to aid in the rational design of novel broad specificity antidotes...
May 10, 2017: Toxins
https://www.readbyqxmd.com/read/28483193/expression-of-complete-siv-p27-gag-and-hiv-gp120-engineered-outer-domains-targeted-by-broadly-neutralizing-antibodies-in-live-rubella-vectors
#14
Konstantin Virnik, Edmund Nesti, Cody Dail, Max Hockenbury, Yisheng Ni, Barbara K Felber, William R Schief, Ira Berkower
Infection with HIV or SIV often elicits a potent immune response to viral antigens. This includes T cells and antibodies specific for Gag and Env antigens. In contrast, when given as a vaccine, the same antigens have been weak immunogens, unable to elicit antibodies with comparable titer, durability, or neutralizing activity. We have used the live attenuated rubella vaccine strain RA27/3 as a viral vector to express HIV and SIV antigens. By mimicking an HIV infection, these vectors could elicit stronger and more durable immunity to HIV antigens...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28472201/predicting-hiv-1-transmission-and-antibody-neutralization-efficacy-in-vivo-from-stoichiometric-parameters
#15
Oliver F Brandenberg, Carsten Magnus, Peter Rusert, Huldrych F Günthard, Roland R Regoes, Alexandra Trkola
The potential of broadly neutralizing antibodies targeting the HIV-1 envelope trimer to prevent HIV-1 transmission has opened new avenues for therapies and vaccines. However, their implementation remains challenging and would profit from a deepened mechanistic understanding of HIV-antibody interactions and the mucosal transmission process. In this study we experimentally determined stoichiometric parameters of the HIV-1 trimer-antibody interaction, confirming that binding of one antibody is sufficient for trimer neutralization...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28472040/ultra-deep-sequencing-reveals-high-prevalence-and-broad-structural-diversity-of-hepatitis-b-surface-antigen-mutations-in-a-global-population
#16
Mikael Gencay, Kirsten Hübner, Peter Gohl, Anja Seffner, Michael Weizenegger, Dionysios Neofytos, Richard Batrla, Andreas Woeste, Hyon-Suk Kim, Gaston Westergaard, Christine Reinsch, Eva Brill, Pham Thi Thu Thuy, Bui Huu Hoang, Mark Sonderup, C Wendy Spearman, Stephan Pabinger, Jérémie Gautier, Giuseppina Brancaccio, Massimo Fasano, Teresa Santantonio, Giovanni B Gaeta, Markus Nauck, Wolfgang E Kaminski
The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents...
2017: PloS One
https://www.readbyqxmd.com/read/28469517/a-little-help-from-the-follicles-understanding-the-germinal-center-response-to-human-immunodeficiency-virus-1-infection-and-prophylactic-vaccines
#17
REVIEW
Ebony N Gary, Michele A Kutzler
Human immunodeficiency virus 1 (HIV-1) is the causative agent of AIDS. There are currently more than 35 million people living with HIV infection worldwide, and more than 2 million new infections occur each year. The global pandemic caused by HIV-1 is the subject of numerous research projects, with the development of a prophylactic vaccine and a therapeutic cure being the ultimate goals. The classic paradigms of vaccinology have proven incapable of producing a viable vaccine due to the complexity of the virus' replication cycle, its genetic diversity, and a lack of understanding of the immune correlates of protection...
2017: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/28469084/broadly-neutralizing-antibodies-with-few-somatic-mutations-and-hepatitis-c-virus-clearance
#18
Justin R Bailey, Andrew I Flyak, Valerie J Cohen, Hui Li, Lisa N Wasilewski, Anna E Snider, Shuyi Wang, Gerald H Learn, Nurgun Kose, Leah Loerinc, Rebecca Lampley, Andrea L Cox, Jennifer M Pfaff, Benjamin J Doranz, George M Shaw, Stuart C Ray, James E Crowe
Here, we report the isolation of broadly neutralizing mAbs (bNAbs) from persons with broadly neutralizing serum who spontaneously cleared hepatitis C virus (HCV) infection. We found that bNAbs from two donors bound the same epitope and were encoded by the same germline heavy chain variable gene segment. Remarkably, these bNAbs were encoded by antibody variable genes with sparse somatic mutations. For one of the most potent bNAbs, these somatic mutations were critical for antibody neutralizing breadth and for binding to autologous envelope variants circulating late in infection...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28466900/synthetic-multivalent-v3-glycopeptides-display-enhanced-recognition-by-glycan-dependent-hiv-1-broadly-neutralizing-antibodies
#19
Hui Cai, Jared Orwenyo, Javier Guenaga, John Giddens, Christian Toonstra, Richard T Wyatt, Lai-Xi Wang
We describe here the synthesis of novel multivalent HIV V3 domain glycopeptides and their binding to broadly neutralizing antibodies PGT128 and 10-1074. Our binding data reveal a distinct mode of antigen recognition by the two antibodies and further suggest that multivalent glycopeptides could mimic the neutralizing epitopes more efficiently than the monomeric glycopeptide.
May 14, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28465158/measles-virus-hemagglutinin-epitopes-immunogenic-in-natural-infection-and-vaccination-are-targeted-by-broad-or-genotype-specific-neutralizing-monoclonal-antibodies
#20
Miguel Angel Muñoz-Alía, José M Casasnovas, María Luisa Celma, Juan Carabaña, Paloma B Liton, Rafael Fernandez-Muñoz
Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia)...
April 29, 2017: Virus Research
keyword
keyword
61265
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"