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Broadly neutralizing antibodies

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https://www.readbyqxmd.com/read/29784645/harnessing-post-translational-modifications-for-next-generation-hiv-immunogens
#1
REVIEW
Joel D Allen, Rogier W Sanders, Katie J Doores, Max Crispin
The extensive post-translational modifications of the envelope spikes of the human immunodeficiency virus (HIV) present considerable challenges and opportunities for HIV vaccine design. These oligomeric glycoproteins typically have over 30 disulfide bonds and around a 100 N-linked glycosylation sites, and are functionally dependent on protease cleavage within the secretory system. The resulting mature structure adopts a compact fold with the vast majority of its surface obscured by a protective shield of glycans which can be targeted by broadly neutralizing antibodies (bnAbs)...
May 21, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29777102/a-virus-like-particle-based-tetravalent-vaccine-for-hand-foot-and-mouth-disease-elicits-broad-and-balanced-protective-immunity
#2
Wei Zhang, Wenlong Dai, Chao Zhang, Yu Zhou, Pei Xiong, Shuxia Wang, Xiaohua Ye, Qingwei Liu, Dongming Zhou, Zhong Huang
Hand, foot, and mouth disease (HFMD) is an infectious disease that mainly affects infants and children, causing considerable morbidity and mortality worldwide. HFMD is commonly caused by enterovirus 71 (EV71) and coxsackieviruses A16 (CVA16), A6 (CVA6), and A10 (CVA10). Formalin-inactivated EV71 vaccines are currently available in China; however, these vaccines fail to confer cross-protection against infections by other HFMD-causing enteroviruses, highlighting the necessity of developing a multivalent HFMD vaccine...
May 18, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29775847/strategies-for-a-multi-stage-neutralizing-antibody-based-hiv-vaccine
#3
REVIEW
Raiees Andrabi, Jinal N Bhiman, Dennis R Burton
A critical property of a prophylactic HIV vaccine is likely to be its ability to elicit broadly neutralizing antibodies (bnAbs). BnAbs typically have multiple unusual features and are generated in a fraction of HIV-infected individuals through complex pathways. Current vaccine design approaches seek to trigger rare B cell precursors and then steer affinity maturation toward bnAbs in a multi-stage multi-component immunization approach. These vaccine design strategies have been facilitated by molecular descriptions of bnAb interactions with stabilized HIV trimers, the use of an array of sophisticated approaches for immunogen design, the development of novel animal models for immunogen evaluation and advanced technologies to interrogate antibody responses...
May 15, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29773829/sequential-immunizations-with-a-panel-of-hiv-1-env-virus-like-particles-coach-immune-system-to-make-broadly-neutralizing-antibodies
#4
Teena Mohan, Zachary Berman, Sang-Moo Kang, Bao-Zhong Wang
Broadly neutralizing antibodies (bnAbs) are correlated with passive HIV/SHIV protection and are desirable components of a HIV protective immunity. In the current study, we have designed a sequential-immunization strategy with a panel of envelope glycoprotein (Env)-enriched virus-like particles (VLPs) from various HIV-1 clades (A-E) to elicit bnAbs with high breadth and potency of neutralization in rabbits. We have compared this regimen with repetitive immunizations of individual Env (subtype B) VLPs or a mixture of various Env VLPs...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768174/hiv-1-vaccines-based-on-antibody-identification-b-cell-ontogeny-and-epitope-structure
#5
REVIEW
Peter D Kwong, John R Mascola
HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural characteristics of these antibodies and the epitopes they recognize is enabling new approaches to vaccine design...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29762173/a-defucosylated-bispecific-multivalent-molecule-exhibits-broad-hiv-1-neutralizing-activity-and-enhanced-adcc-against-reactivated-hiv-1-latently-infected-cells
#6
Desheng Kong, Yan Wang, Ping Ji, Wei Li, Tianlei Ying, Jinghe Huang, Chen Wang, Yanling Wu, Yanping Wang, Weizao Chen, Yanling Hao, Kunxue Hong, Yiming Shao, Dimiter S Dimitrov, Shibo Jiang, Liying Ma
OBJECTIVE: Current treatments cannot completely eradicate HIV-1 owing to the presence of latently infected cells which harbor transcriptionally silent HIV-1. However, defucosylated antibodies can readily kill latently infected cells after their activation to express envelope glycoprotein (Env) through antibody-dependent cellular cytotoxicity (ADCC). We herein aimed to test a defucosylated bispecific multivalent molecule consisting of domain-antibody and single-domain CD4, LSEVh-LS-F, for its HIV-1 neutralizing activity and ADCC against the reactivated latently infected cells, compared with the non-defucosylated molecule LSEVh-LS...
May 11, 2018: AIDS
https://www.readbyqxmd.com/read/29760533/cross-specificity-of-protective-human-antibodies-against-klebsiella-pneumoniae-lps-o-antigen
#7
Tim Rollenske, Valeria Szijarto, Jolanta Lukasiewicz, Luis M Guachalla, Katarina Stojkovic, Katharina Hartl, Lukas Stulik, Simone Kocher, Felix Lasitschka, Mohammed Al-Saeedi, Jutta Schröder-Braunstein, Moritz von Frankenberg, Gereon Gaebelein, Peter Hoffmann, Sabrina Klein, Klaus Heeg, Eszter Nagy, Gabor Nagy, Hedda Wardemann
Humoral immune responses to microbial polysaccharide surface antigens can prevent bacterial infection but are typically strain specific and fail to mediate broad protection against different serotypes. Here we describe a panel of affinity-matured monoclonal human antibodies from peripheral blood immunoglobulin M-positive (IgM+ ) and IgA+ memory B cells and clonally related intestinal plasmablasts, directed against the lipopolysaccharide (LPS) O-antigen of Klebsiella pneumoniae, an opportunistic pathogen and major cause of antibiotic-resistant nosocomial infections...
May 14, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29759530/emerging-glycobiology-tools-a-renaissance-in-accessibility
#8
REVIEW
Douglas M Oswald, Brian A Cobb
The glycobiology of the immune response is a topic that has garnered increased attention due to a number of key discoveries surrounding IgG function, the specificity of some broadly neutralizing anti-HIV antibodies, cancer immunoregulation by galectin molecules and others. This review is the opening article in a Special Edition of Cellular Immunology focused on glycoimmunology, and has the goal of setting the context for these articles by providing a mini-review of how glycans impact immunity. We also focus on some of the technological and methodological advances in the field of glycobiology that are being deployed to lower the barrier of entry into the glycosciences, and to more fully interrogate the glycome and its function...
April 25, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29746590/structural-and-immunologic-correlates-of-chemically-stabilized-hiv-1-envelope-glycoproteins
#9
Torben Schiffner, Jesper Pallesen, Rebecca A Russell, Jonathan Dodd, Natalia de Val, Celia C LaBranche, David Montefiori, Georgia D Tomaras, Xiaoying Shen, Scarlett L Harris, Amin E Moghaddam, Oleksandr Kalyuzhniy, Rogier W Sanders, Laura E McCoy, John P Moore, Andrew B Ward, Quentin J Sattentau
Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects structure, antigenicity and immunogenicity is poorly understood and its use remains entirely empirical. We have solved the first cryo-EM structure of a cross-linked vaccine antigen. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a CD4 binding site-specific broadly neutralizing antibody (bNAb) Fab fragment reveals how cross-linking affects key properties of the trimer...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29743371/roles-of-fc-domain-and-exudation-in-l2-antibody-mediated-protection-against-human-papillomavirus
#10
Joshua W Wang, Wai Hong Wu, Tsui-Chin Huang, Margaret Wong, Kihyuck Kwak, Keiko Ozato, Chien-Fu Hung, Richard B S Roden
To address how L2-specific antibodies prevent human papillomavirus (HPV) infection of the genital tract we generated neutralizing monoclonal antibodies (MAbs) WW1, a rat IgG2a that binds L2 residues 17-36 (like mouse MAb RG1), and JWW3, a mouse IgG1 derivative of Mab24 specific to L2 residues 58-64. By Western blot, WW1 recognized L2 of 29/34 HPV genotypes tested, compared to only 13/34 for RG1, and 25/34 for JWW3. WW1 IgG and (Fab')2 bound HPV16 pseudovirions similarly, however whole IgG provided better protection against HPV vaginal challenge...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29740451/therapeutic-administration-of-broadly-neutralizing-fi6-antibody-reveals-lack-of-interaction-between-human-igg1-and-pig-fc-receptors
#11
Sophie B Morgan, Barbara Holzer, Johanneke D Hemmink, Francisco J Salguero, John C Schwartz, Gloria Agatic, Elisabetta Cameroni, Barbara Guarino, Emily Porter, Pramila Rijal, Alain Townsend, Bryan Charleston, Davide Corti, Elma Tchilian
Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1-H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740424/modulation-of-dengue-zika-virus-pathogenicity-by-antibody-dependent-enhancement-and-strategies-to-protect-against-enhancement-in-zika-virus-infection
#12
REVIEW
Rekha Khandia, Ashok Munjal, Kuldeep Dhama, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal Singh Malik, Raj Kumar Singh, Wanpen Chaicumpa
Antibody-dependent enhancement (ADE) is a phenomenon in which preexisting poorly neutralizing antibodies leads to enhanced infection. It is a serious concern with mosquito-borne flaviviruses such as Dengue virus (DENV) and Zika virus (ZIKV). In vitro experimental evidences have indicated the preventive, as well as a pathogenicity-enhancing role, of preexisting DENV antibodies in ZIKV infections. ADE has been confirmed in DENV but not ZIKV infections. Principally, the Fc region of the anti-DENV antibody binds with the fragment crystallizable gamma receptor (FcγR), and subsequent C1q interactions and immune effector functions are responsible for the ADE...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738673/top-down-chemoenzymatic-approach-to-synthesizing-diverse-high-mannose-n-glycans-and-related-neoglycoproteins-for-carbohydrate-microarray-analysis
#13
Christian Toonstra, Lisa Wu, Chao Li, Denong Wang, Lai-Xi Wang
High mannose type N-glycans are an important component of neutralizing epitopes on HIV-1 envelope glycoprotein gp120. They also serve as signals for protein folding, trafficking, and degradation in protein quality control. A number of lectins and antibodies recognize high-mannose type N-glycans, and glycan array technology has provided an avenue to probing these oligomannose-specific proteins. We describe in this paper a top-down chemoenzymatic approach to synthesizing a library of high-mannose N-glycans and related neoglycoproteins for glycan microarray analysis...
May 8, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29736600/investigation-of-sequence-clipping-and-structural-heterogeneity-of-an-hiv-broadly-neutralizing-antibody-by-a-comprehensive-lc-ms-analysis
#14
Vera B Ivleva, Nicole A Schneck, Deepika Gollapudi, Frank Arnold, Jonathan W Cooper, Q Paula Lei
CAP256 is one of the highly potent, broadly neutralizing monoclonal antibodies (bNAb) designed for HIV-1 therapy. During the process development of one of the constructs, an unexpected product-related impurity was observed via microfluidics gel electrophoresis. A panel of complementary LC-MS analyses was applied for the comprehensive characterization of CAP256 which included the analysis of the intact and reduced protein, the middle-up approach, and a set of complementary peptide mapping techniques and verification of the disulfide bonds...
May 7, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29736037/broadly-neutralizing-antibodies-from-human-survivors-target-a-conserved-site-in-the-ebola-virus-glycoprotein-hr2-mper-region
#15
Andrew I Flyak, Natalia Kuzmina, Charles D Murin, Christopher Bryan, Edgar Davidson, Pavlo Gilchuk, Christopher P Gulka, Philipp A Ilinykh, Xiaoli Shen, Kai Huang, Palaniappan Ramanathan, Hannah Turner, Marnie L Fusco, Rebecca Lampley, Nurgun Kose, Hannah King, Gopal Sapparapu, Benjamin J Doranz, Thomas G Ksiazek, David W Wright, Erica Ollmann Saphire, Andrew B Ward, Alexander Bukreyev, James E Crowe
Ebola virus (EBOV) in humans causes a severe illness with high mortality rates. Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection 1 and has been used under compassionate-treatment protocols in humans 2 . ZMapp is a mixture of three chimerized murine monoclonal antibodies (mAbs)3-6 that target EBOV-specific epitopes on the surface glycoprotein7,8 . However, ZMapp mAbs do not neutralize other species from the genus Ebolavirus, such as Bundibugyo virus (BDBV), Reston virus (RESTV) or Sudan virus (SUDV)...
May 7, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/29734023/influenza-vaccines-tailor-made-or-one-fits-all
#16
REVIEW
Giulietta Saletti, Thomas Gerlach, Guus F Rimmelzwaan
Currently used inactivated influenza vaccines aim at the induction of virus-neutralizing antibodies directed to the variable head domain of the viral hemagglutinin. Although these vaccines are effective against antigenically matching virus strains, they offer little protection against antigenically distinct drift variants or potentially pandemic viruses of alternative subtypes. In the last decades, the threat of novel influenza pandemics has sparked research efforts to develop vaccines that induce more broadly protective immunity...
May 4, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29731169/identification-of-near-pan-neutralizing-antibodies-against-hiv-1-by-deconvolution-of-plasma-humoral-responses
#17
Mohammad Mohseni Sajadi, Amir Dashti, Zahra Rikhtegaran Tehrani, William D Tolbert, Michael S Seaman, Xin Ouyang, Neelakshi Gohain, Marzena Pazgier, Dongkyoon Kim, Guy Cavet, Jean Yared, Robert R Redfield, George K Lewis, Anthony L DeVico
Anti-HIV-1 envelope broadly neutralizing monoclonal antibodies (bNAbs) isolated from memory B cells may not fully represent HIV-1-neutralizing profiles measured in plasma. Accordingly, we characterized near-pan-neutralizing antibodies extracted directly from the plasma of two "elite neutralizers." Circulating anti-gp120 polyclonal antibodies were deconvoluted using proteomics to guide lineage analysis of bone marrow plasma cells. In both subjects, a single lineage of anti-CD4-binding site (CD4bs) antibodies explained the plasma-neutralizing activity...
April 28, 2018: Cell
https://www.readbyqxmd.com/read/29718999/glycoengineering-hiv-1-env-creates-supercharged-and-hybrid-glycans-to-increase-neutralizing-antibody-potency-breadth-and-saturation
#18
Ema T Crooks, Samantha L Grimley, Michelle Cully, Keiko Osawa, Gillian Dekkers, Kevin Saunders, Sebastian Rӓmisch, Sergey Menis, William R Schief, Nicole Doria-Rose, Barton Haynes, Ben Murrell, Evan Mitchel Cale, Amarendra Pegu, John R Mascola, Gestur Vidarsson, James M Binley
The extensive glycosylation of HIV-1 envelope (Env) glycoprotein leaves few glycan-free holes large enough to admit broadly neutralizing antibodies (bnAb). Consequently, most bnAbs must inevitably make some glycan contacts and avoid clashes with others. To investigate how Env glycan maturation regulates HIV sensitivity to bnAbs, we modified HIV-1 pseudovirus (PV) using various glycoengineering (GE) tools. Promoting the maturation of α-2,6 sialic acid (SA) glycan termini increased PV sensitivity to two bnAbs that target the V2 apex and one to the interface between Env surface gp120 and transmembrane gp41 subunits, typically by up to 30-fold...
May 2, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29718555/treatment-with-broadly-neutralizing-influenza-antibodies-reduces-severity-of-secondary-pneumococcal-pneumonia-in-mice
#19
Frank van Someren Gréve, Koenraad F van der Sluijs, Anita M Tuip, Marcus J Schultz, Menno D de Jong, Nicole P Juffermans
BACKGROUND: Secondary bacterial pneumonia is a frequent complication of influenza, associated with high morbidity and mortality. We hypothesized that treatment with neutralizing influenza A antibody AT10_002 protects against severe secondary pneumococcal infection in a mouse model of influenza A infection. METHODS: Influenza A (H3N2) virus-infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control two days post-infection. Seven days later both groups were infected with Streptococcus pneumoniae, and sacrificed 18 hours later...
May 2, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29703495/can-broadly-neutralizing-monoclonal-antibodies-lead-to-a-hepatitis-c-virus-vaccine
#20
REVIEW
Valerie J Kinchen, Andrea L Cox, Justin R Bailey
While licensed vaccines elicit protective antibody responses against a variety of viral infections, an effective vaccine for hepatitis C virus (HCV) has remained elusive. The extraordinary genetic diversity of HCV and the ability of the virus to evade the immune response have hindered vaccine development efforts. However, recent studies have greatly expanded the number of well characterized broadly neutralizing human monoclonal antibodies (bNAbs) against HCV. These bNAbs target relatively conserved HCV epitopes, prevent HCV infection in animal models, and are associated with spontaneous clearance of human HCV infection...
April 24, 2018: Trends in Microbiology
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