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Broadly neutralizing antibody

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https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#1
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28102191/a-broadly-protective-therapeutic-antibody-against-influenza-b-virus-with-two-mechanisms-of-action
#2
Ning Chai, Lee R Swem, Summer Park, Gerald Nakamura, Nancy Chiang, Alberto Estevez, Rina Fong, Lynn Kamen, Elviza Kho, Mike Reichelt, Zhonghua Lin, Henry Chiu, Elizabeth Skippington, Zora Modrusan, Jeremy Stinson, Min Xu, Patrick Lupardus, Claudio Ciferri, Man-Wah Tan
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28100831/coexistence-of-potent-hiv-1-broadly-neutralizing-antibodies-and-antibody-sensitive-viruses-in-a-viremic-controller
#3
Natalia T Freund, Haoqing Wang, Louise Scharf, Lilian Nogueira, Joshua A Horwitz, Yotam Bar-On, Jovana Golijanin, Stuart A Sievers, Devin Sok, Hui Cai, Julio C Cesar Lorenzi, Ariel Halper-Stromberg, Ildiko Toth, Alicja Piechocka-Trocha, Harry B Gristick, Marit J van Gils, Rogier W Sanders, Lai-Xi Wang, Michael S Seaman, Dennis R Burton, Anna Gazumyan, Bruce D Walker, Anthony P West, Pamela J Bjorkman, Michel C Nussenzweig
Some HIV-1-infected patients develop broad and potent HIV-1 neutralizing antibodies (bNAbs) that when passively transferred to mice or macaques can treat or prevent infection. However, bNAbs typically fail to neutralize coexisting autologous viruses due to antibody-mediated selection against sensitive viral strains. We describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. Neutralization was attributed to three different bNAbs targeting nonoverlapping sites on the HIV-1 envelope trimer (Env)...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28100617/differences-in-glycoprotein-complex-gpc-receptor-binding-site-accessibility-prompt-poor-cross-reactivity-of-neutralizing-antibodies-between-closely-related-arenaviruses
#4
Rachel B Brouillette, Elisabeth K Phillips, Natarajan Ayithan, Wendy Maury
: The glycoprotein complex (GPC) of arenaviruses, composed of stable signal peptide (SSP), GP1, and GP2, is the only antigen correlated with antibody-mediated neutralization. However, despite strong cross-reactivity of convalescent antisera between related arenavirus species, weak or no cross-neutralization occurs. Two closely related Clade B viruses, Machupo virus (MACV) and Junín virus (JUNV), have near identical overall GPC architecture and share a host receptor, transferrin receptor 1...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#5
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
: Interferon inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates including transmitted founder viruses is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28099492/priming-cross-protective-bovine-viral-diarrhea-virus-specific-immunity-using-live-vectored-mosaic-antigens
#6
Shehnaz Lokhandwala, Xin Fang, Suryakant D Waghela, Jocelyn Bray, Leo M Njongmeta, Andy Herring, Karim W Abdelsalam, Christopher Chase, Waithaka Mwangi
Bovine viral diarrhea virus (BVDV) plays a key role in bovine respiratory disease complex, which can lead to pneumonia, diarrhea and death of calves. Current vaccines are not very effective due, in part, to immunosuppressive traits and failure to induce broad protection. There are diverse BVDV strains and thus, current vaccines contain representative genotype 1 and 2 viruses (BVDV-1 & 2) to broaden coverage. BVDV modified live virus (MLV) vaccines are superior to killed virus vaccines, but they are susceptible to neutralization and complement-mediated destruction triggered by passively acquired antibodies, thus limiting their efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#7
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28090318/dengue-virus-antibodies-enhance-zika-virus-infection
#8
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Scott F Michael, Sharon Isern
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28088708/germinal-centers-programmed-for-affinity-maturation-and-antibody-diversification
#9
REVIEW
Oliver Bannard, Jason G Cyster
The seminal discovery by Eisen that antibodies undergo improvements in antigen-binding affinity over the course of an immune response led to a long running search for the underlying mechanism. Germinal centers in lymphoid organs are now recognized to be critically involved in this phenomenon, known as antibody affinity maturation. As well as improving in affinity for specific epitopes, some antibody responses maintain or even increase their breadth of antigen-recognition over time. This has led to another intense line of research aimed at understanding how broadly neutralizing anti-pathogen responses are generated...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088123/antibody-dependent-cellular-cytotoxicity-and-influenza-virus
#10
REVIEW
Hillary A Vanderven, Sinthujan Jegaskanda, Adam K Wheatley, Stephen J Kent
Antibodies are a key defence against influenza infection and disease, but neutralizing antibodies are often strain-specific and of limited utility against divergent or pandemic viruses. There is now considerable evidence that influenza-specific antibodies with Fc-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can assist in the clearance of influenza infection in vitro and in animal models. Further, ADCC-mediating antibodies that recognize a broad array of influenza strains are common in humans, likely as a result of being regularly exposed to influenza infections...
January 11, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28077656/hierarchical-and-redundant-roles-of-activating-fc%C3%AE-rs-in-protection-against-influenza-disease-by-m2e-specific-igg1-and-igg2a-antibodies
#11
Silvie Van den Hoecke, Katrin Ehrhardt, Annasaheb Kolpe, Karim El Bakkouri, Lei Deng, Hendrik Grootaert, Steve Schoonooghe, Anouk Smet, Mostafa Bentahir, Kenny Roose, Michael Schotsaert, Bert Schepens, Nico Callewaert, Falk Nimmerjahn, Peter Staeheli, Hartmut Hengel, Xavier Saelens
: The ectodomain of matrix protein 2 is a universal influenza A vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ Receptor family members by two M2e-specific monoclonal antibodies: mAb 37 (IgG1) and mAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinity. Binding of mAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas mAb 37 only activated FcγRIII...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077654/neutralization-of-diverse-human-cytomegalovirus-strains-conferred-by-antibodies-targets-viral-gh-gl-pul128-131-pentameric-complex
#12
Sha Ha, Fengsheng Li, Matthew C Troutman, Daniel C Freed, Aimin Tang, John W Loughney, Dai Wang, I-Ming Wang, Josef Vlasak, David C Nickle, Richard R Rustandi, Melissa Hamm, Pete A DePhillips, Ningyan Zhang, Jason S McLellan, Hua Zhu, Stuart P Adler, Michael A McVoy, Zhiqiang An, Tong-Ming Fu
: Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and developing a prophylactic vaccine is of high priority to public health. We recently reported a replication-defective human cytomegalovirus with restored pentameric complex gH/gL/pUL128-131 for prevention of congenital HCMV infection. While the quantity of vaccine-induced antibody responses can be measured in a viral neutralization assay, assessing the quality of such responses, including the ability of vaccine-induced antibodies to cross neutralize the field strains of HCMV, remains a challenge...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077631/vaccine-efficacy-of-an-inactivated-chimeric-ha-h9-h5n2-avian-influenza-virus-and-its-suitability-for-the-marker-vaccine-strategy
#13
Se Mi Kim, Young-Il Kim, Su-Jin Park, Eun-Ha Kim, Hyeok-Il Kwon, Young-Jae Si, In-Won Lee, Min-Suk Song, Young Ki Choi
: In order to produce a dual effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine which expressed the whole HA1 region of A/CK/Korea/04163/04 H9N2 and HA2 region of recent HPAI A/MD/Korea/W452/14 H5N8 viruses. The Chimeric H9/H5N2 virus showed similar in vitro and in vivo growth properties and virulence to the LPAI H9 influenza virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses, but only induced cross-reactive hemmaglutination inhibition (HI) antibody against H9 viruses...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076415/structure-and-recognition-of-a-novel-hiv-1-gp120-gp41-interface-antibody-that-caused-mper-exposure-through-viral-escape
#14
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N Bhiman, Daniel J Sheward, Debra H Elliott, Julie Rouelle, Ashley Smira, M Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R Burton, Mark Connors, Salim S Abdool Karim, John R Mascola, James E Robinson, Andrew B Ward, Carolyn Williamson, Peter D Kwong, Lynn Morris, Penny L Moore
A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28073404/isolation-and-characterization-of-hiv-1-envelope-glycoprotein-specific-b-cell-from-immortalized-human-na%C3%A3-ve-b-cell-library
#15
Zehua Sun, Shiqiang Lu, Zheng Yang, Jingjing Li, Meiyun Zhang
With the recent development of single B cell cloning techniques, an increasing number of HIV-1-specific broadly neutralizing antibodies (bNAbs) have been isolated since 2009. However, knowledge regarding HIV-1-specific B cells in vivo is limited. In this study, an HIV-1-specific B cell line has been established using healthy PBMC donors by the highly efficient EBV transformation method to generate immortalized human naïve B cell libraries. The enrichment of HIV-1 envelope-specific B cells was observed after four rounds of cell panning with the HIV-1 envelope glycoprotein...
January 10, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28065804/limited-naturally-occurring-escape-in-broadly-neutralizing-antibody-epitopes-in-hepatitis-c-glycoprotein-e2-and-constrained-sequence-usage-in-acute-infection
#16
Chaturaka Rodrigo, Melanie R Walker, Preston Leung, Auda A Eltahla, Jason Grebely, Gregory J Dore, Tanya Applegate, Kimberly Page, Sunita Dwivedi, Julie Bruneau, Meghan D Morris, Andrea L Cox, William Osburn, Arthur Y Kim, Janke Schinkel, Naglaa H Shoukry, Georg M Lauer, Lisa Maher, Margaret Hellard, Maria Prins, Fabio Luciani, Andrew R Lloyd, Rowena A Bull
Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved regions for vaccine design. All reported broadly neutralizing antibody (BNAb) epitopes in the HCV Envelope (E2) glycoprotein were identified. The critical contact residues of these epitopes were mapped onto the linear E2 sequence...
January 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28062126/cross-reactivity-of-immune-responses-to-porcine-reproductive-and-respiratory-syndrome-virus-infection
#17
Ignacio Correas, Fernando A Osorio, David Steffen, Asit K Pattnaik, Hiep L X Vu
Because porcine reproductive and respiratory syndrome virus (PRRSV) exhibits extensive genetic variation among field isolates, characterizing the extent of cross reactivity of immune responses, and most importantly cell-mediated immunity (CMI), could help in the development of broadly cross-protective vaccines. We infected 12 PRRSV-naïve pigs with PRRSV strain FL12 and determined the number of interferon (IFN)-γ secreting cells (SC) by ELISpot assay using ten type 2 and one type 1 PRRSV isolates as recall antigens...
January 3, 2017: Vaccine
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#18
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28052137/mapping-polyclonal-hiv-1-antibody-responses-via-next-generation-neutralization-fingerprinting
#19
Nicole A Doria-Rose, Han R Altae-Tran, Ryan S Roark, Stephen D Schmidt, Matthew S Sutton, Mark K Louder, Gwo-Yu Chuang, Robert T Bailer, Valerie Cortez, Rui Kong, Krisha McKee, Sijy O'Dell, Felicia Wang, Salim S Abdool Karim, James M Binley, Mark Connors, Barton F Haynes, Malcolm A Martin, David C Montefiori, Lynn Morris, Julie Overbaugh, Peter D Kwong, John R Mascola, Ivelin S Georgiev
Computational neutralization fingerprinting, NFP, is an efficient and accurate method for predicting the epitope specificities of polyclonal antibody responses to HIV-1 infection. Here, we present next-generation NFP algorithms that substantially improve prediction accuracy for individual donors and enable serologic analysis for entire cohorts. Specifically, we developed algorithms for: (a) selection of optimized virus neutralization panels for NFP analysis, (b) estimation of NFP prediction confidence for each serum sample, and (c) identification of sera with potentially novel epitope specificities...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28031364/an-optimized-hepatitis-c-virus-e2-glycoprotein-core-adopts-a-functional-homodimer-that-efficiently-blocks-virus-entry
#20
Kathleen McCaffrey, Irene Boo, Catherine M Owczarek, Matthew P Hardy, Matthew A Perugini, Louis Fabri, Pierre Scotney, Pantelis Poumbourios, Heidi E Drummer
: The hepatitis C virus (HCV) envelope glycoprotein E2 is the major target of broadly neutralizing antibodies in vivo and is the focus of efforts in the rational design of a universal B cell vaccine against HCV. The E2 glycoprotein exhibits a high degree of amino-acid variability which localizes to three discrete regions: hypervariable region 1 (HVR1), hypervariable region 2 (HVR2) and the intergenotypic variable region (igVR). All three variable regions contribute to immune evasion and/or isolate-specific structural variations, both important considerations for vaccine design...
December 28, 2016: Journal of Virology
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