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https://www.readbyqxmd.com/read/28422789/antigp41-membrane-proximal-external-region-antibodies-and-the-art-of-using-the-membrane-for-neutralization
#1
Nichole Cerutti, Juan Luis Loredo-Varela, Christophe Caillat, Winfried Weissenhorn
PURPOSE OF REVIEW: We summarize the latest research on the progress to understand the neutralizing epitopes present within the membrane proximal external region (MPER) of the HIV-1 fusion protein subunit gp41. RECENT FINDINGS: The HIV-1 fusion protein subunit gp41 contains a highly conserved sequence that is essential for membrane fusion and targeted by broadly neutralizing antibodies such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41 epitope with high affinity, but require additional hydrophobic sequences present in their heavy chain CDR3 for neutralization...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28395728/-preparation-and-characterization-of-monoclonal-antibody-against-gp120-v1-v2-domain-of-hiv-1-subtype-crf01_ae
#2
Ying Chu, Xiangdan Gong, Jianwei Gao, Airong Su, Deyan Chen, Hongyong Song, Xilin Wu, Zhiwei Wu
Objective To express the V1/V2 domain of HIV-1 subtype CRF01_AE gp120 in eukaryotic cells, and then prepare its monoclonal antibody (mAb) and identify its antigen reactivity. Methods Eukaryotic expression vector of pTriEx-3-V1/V2CNE55 was constructed and transiently transfected into HEK293F cell line. The V1/V2-His chimera protein was purified and injected into BALB/c mice. After the fusion between spleen cells of immunized BALB/c mice and myeloma cells SP 2/0, ELISA was used for screening the positive hybridoma cell clones against the V1/V2 recombinant protein...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28358050/antibody-dependent-cellular-cytotoxicity-inducing-antibodies-significantly-affect-the-post-exposure-treatment-of-ebola-virus-infection
#3
Qiang Liu, Changfa Fan, Qianqian Li, Shuya Zhou, Weijin Huang, Lan Wang, Chunyun Sun, Meng Wang, Xi Wu, Jian Ma, Baowen Li, Liangzhi Xie, Youchun Wang
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351688/performance-of-serological-and-molecular-tests-within-acute-hiv-infection
#4
Katrien Fransen, Irith de Baetselier, Elizabeth Rammutla, Khatija Ahmed, Frederick Owino, Walter Agingu, Gustav Venter, Jen Deese, Lut Van Damme, Tania Crucitti
BACKGROUND: Early diagnosis of acute HIV infection can be challenging and is critical in regards to early therapeutic decision making. OBJECTIVES: To evaluate the performance of different HIV tests in detecting early infections. STUDY DESIGN: A total of 83 leftover specimens of 61 study participants who seroconverted were used in this sub-study. 35 HIV RNA positive but still seronegative specimens (acute infections) were used for analysis of the sensitivity of the different assays in detecting early infections and 42 HIV RNA and antibody negative specimens were used for specificity analysis...
March 21, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
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
#5
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/28207485/antigp41-membrane-proximal-external-region-antibodies-and-the-art-of-using-the-membrane-for-neutralization
#6
Nichole Cerutti, Juan Luis Loredo-Varela, Christophe Caillat, Winfried Weissenhorn
PURPOSE OF REVIEW: We summarize the latest research on the progress to understand the neutralizing epitopes present within the membrane proximal external region (MPER) of the HIV-1 fusion protein subunit gp41. RECENT FINDINGS: The HIV-1 fusion protein subunit gp41 contains a highly conserved sequence that is essential for membrane fusion and targeted by broadly neutralizing antibodies such as 2F5, 4E10, Z13e1, and 10E8. These antibodies recognize a linear gp41 epitope with high affinity, but require additional hydrophobic sequences present in their heavy chain CDR3 for neutralization...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28185743/differential-induction-of-anti-v3-crown-antibodies-with-cradle-and-ladle-binding-modes-in-response-to-hiv-1-envelope-vaccination
#7
Preetha Balasubramanian, Rajnish Kumar, Constance Williams, Vincenza Itri, Shixia Wang, Shan Lu, Ann J Hessell, Nancy L Haigwood, Faruk Sinangil, Keith W Higgins, Lily Liu, Liuzhe Li, Phillipe Nyambi, Miroslaw K Gorny, Maxim Totrov, Arthur Nadas, Xiang-Peng Kong, Susan Zolla-Pazner, Catarina E Hioe
The V3 loop in the HIV envelope gp120 is one of the immunogenic sites targeted by Abs. The V3 crown in particular has conserved structural elements recognized by cross-reactive neutralizing Abs, indicating its potential contribution in protection against HIV. Crystallographic analyses of anti-V3 crown mAbs in complex with the V3 peptides have revealed that these mAbs recognize the conserved sites on the V3 crown via two distinct strategies: a cradle-binding mode (V3C) and a ladle-binding (V3L) mode. However, almost all of the anti-V3 crown mAbs studied in the past were isolated from chronically HIV-infected individuals...
March 7, 2017: Vaccine
https://www.readbyqxmd.com/read/28177967/neutralizing-and-targeting-properties-of-a-new-set-of-%C3%AE-4%C3%AE-7-specific-antibodies-are-influenced-by-their-isotype
#8
Alexandre Girard, Katija Jelicic, Don Van Ryk, Nicolas Rochereau, Claudia Cicala, James Arthos, Blandine Noailly, Christian Genin, Bernard Verrier, Stephanie Laurant, Diane Razanajaoana-Doll, Jean-Jacques Pin, Stéphane Paul
The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells...
May 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28133803/use-of-broadly-neutralizing-antibodies-for-hiv-1-prevention
#9
REVIEW
Amarendra Pegu, Ann J Hessell, John R Mascola, Nancy L Haigwood
Antibodies have a long history in antiviral therapy, but until recently, they have not been actively pursued for HIV-1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV-1 isolates have reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV-1...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28122974/monoclonal-antibodies-specific-for-the-v2-v3-cd4-binding-site-and-gp41-of-hiv-1-mediate-phagocytosis-in-a-dose-dependent-manner
#10
Thomas Musich, Liuzhe Li, Lily Liu, Susan Zolla-Pazner, Marjorie Robert-Guroff, Miroslaw K Gorny
In light of the weak or absent neutralizing activity mediated by anti-V2 monoclonal antibodies (MAbs), we tested whether they can mediate Ab-dependent cellular phagocytosis (ADCP), which is an important element of anti-HIV-1 immunity. We tested six anti-V2 MAbs and compared them with 21 MAbs specific for V3, the CD4-binding site (CD4bs), and gp41 derived from chronically HIV-1-infected individuals and produced by hybridoma cells. ADCP activity was measured by flow cytometry using uptake by THP-1 monocytic cells of fluorescent beads coated with gp120, gp41, BG505 SOSIP...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27996375/trimeric-gp120-specific-bovine-monoclonal-antibodies-require-cysteine-and-aromatic-residues-in-cdrh3-for-high-affinity-binding-to-hiv-env
#11
Behnaz Heydarchi, Rob J Center, Jonathan Bebbington, Jack Cuthbertson, Christopher Gonelli, Georges Khoury, Charlene Mackenzie, Marit Lichtfuss, Grant Rawlin, Brian Muller, Damian Purcell
We isolated HIV-1 Envelope (Env)-specific memory B cells from a cow that had developed high titer polyclonal immunoglobulin G (IgG) with broad neutralizing activity after a long duration vaccination with HIV-1AD8 Env gp140 trimers. We cloned the bovine IgG matched heavy (H) and light (L) chain variable (V) genes from these memory B cells and constructed IgG monoclonal antibodies (mAbs) with either a human constant (C)-region/bovine V-region chimeric or fully bovine C and V regions. Among 42 selected Ig+ memory B cells, two mAbs (6A and 8C) showed high affinity binding to gp140 Env...
April 2017: MAbs
https://www.readbyqxmd.com/read/27939012/immunofocusing-using-conformationally-constrained-v3-peptide-immunogens-improves-hiv-1-neutralization
#12
Adi Moseri, Eshu Sinha, Henni Zommer, Boris Arshava, Fred Naider, Jacob Anglister
V3-directed antibodies are present in practically all HIV-1 infected patients and in individuals vaccinated with gp120. The levels of maternal V3-directed antibodies were recently shown to correlate with reduced mother to child transmission, and V3 IgGs were found to be a negative correlate of risk in the RV-144 human trial. mAb directed to the tip of the V3 are capable of broad neutralization of Tier-1 and some Tier-2 viruses. Here we report an immunofocusing approach using conformationally constrained V3 peptides of different lengths...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/27913647/diversity-of-antiviral-igg-effector-activities-observed-in-hiv-infected-and-vaccinated-subjects
#13
Yunda Huang, Guido Ferrari, Galit Alter, Donald N Forthal, John C Kappes, George K Lewis, J Christopher Love, Bhavesh Borate, Linda Harris, Kelli Greene, Hongmei Gao, Tran B Phan, Gary Landucci, Brittany A Goods, Karen G Dowell, Hao D Cheng, Chris Bailey-Kellogg, David C Montefiori, Margaret E Ackerman
Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIV Ab effector activities in polyclonal serum samples from HIV-infected donors, VAX004 vaccine recipients, and healthy HIV-negative subjects using a variety of primary and cell line-based assays, including Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cell-mediated viral inhibition, and Ab-dependent cellular phagocytosis...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27852851/identification-of-human-anti-hiv-gp160-monoclonal-antibodies-that-make-effective-immunotoxins
#14
Seth H Pincus, Kejing Song, Grace A Maresh, Dean H Hamer, Dimiter S Dimitrov, Weizao Chen, Mei-Yun Zhang, Victor F Ghetie, Po-Ying Chan-Hui, James E Robinson, Ellen S Vitetta
The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27815444/an-hiv-1-env-antibody-complex-focuses-antibody-responses-to-conserved-neutralizing-epitopes
#15
Yajing Chen, Richard Wilson, Sijy O'Dell, Javier Guenaga, Yu Feng, Karen Tran, Chi-I Chiang, Heather E Arendt, Joanne DeStefano, John R Mascola, Richard T Wyatt, Yuxing Li
Elicitation of broadly neutralizing Ab (bNAb) responses to the conserved elements of the HIV-1 envelope glycoproteins (Env), including the primary receptor CD4 binding site (CD4bs), is a major focus of vaccine development yet to be accomplished. However, a large number of CD4bs-directed bNAbs have been isolated from HIV-1-infected individuals. Comparison of the routes of binding used by the CD4bs-directed bNAbs from patients and the vaccine-elicited CD4bs-directed mAbs indicates that the latter fail to neutralize primary virus isolates because they approach the Env spike with a vertical angle and contact the specific surface residues occluded in the native spike, including the bridging sheet on gp120...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795412/design-and-in-vivo-characterization-of-immunoconjugates-targeting-hiv-gp160
#16
Seth H Pincus, Kejing Song, Grace A Maresh, Anderson Frank, David Worthylake, Hye-Kyung Chung, Patricia Polacino, Dean H Hamer, Cody P Coyne, Michael G Rosenblum, John W Marks, Gang Chen, Deborah Weiss, Victor Ghetie, Ellen S Vitetta, James E Robinson, Shiu-Lok Hu
The envelope (Env) glycoprotein of HIV is expressed on the surface of productively infected cells and can be used as a target for cytotoxic immunoconjugates (ICs), in which cell-killing moieties, including toxins, drugs, or radionuclides, are chemically or genetically linked to monoclonal antibodies (MAbs) or other targeting ligands. Such ICs could be used to eliminate persistent reservoirs of HIV infection. We have found that MAbs which bind to the external loop of gp41, e.g., MAb 7B2, make highly effective ICs, particularly when used in combination with soluble CD4...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27788205/a-cinnamon-derived-procyanidin-compound-displays-anti-hiv-1-activity-by-blocking-heparan-sulfate-and-co-receptor-binding-sites-on-gp120-and-reverses-t-cell-exhaustion-via-impeding-tim-3-and-pd-1-upregulation
#17
Bridgette Janine Connell, Sui-Yuan Chang, Ekambaranellore Prakash, Rahima Yousfi, Viswaraman Mohan, Wilfried Posch, Doris Wilflingseder, Christiane Moog, Eiichi N Kodama, Pascal Clayette, Hugues Lortat-Jacob
Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range...
2016: PloS One
https://www.readbyqxmd.com/read/27725635/envelope-specific-antibodies-and-antibody-derived-molecules-for-treating-and-curing-hiv-infection
#18
REVIEW
Guido Ferrari, Barton F Haynes, Scott Koenig, Jeffrey L Nordstrom, David M Margolis, Georgia D Tomaras
HIV-1 is a retrovirus that integrates into host chromatin and can remain transcriptionally quiescent in a pool of immune cells. This characteristic enables HIV-1 to evade both host immune responses and antiretroviral drugs, leading to persistent infection. Upon reactivation of proviral gene expression, HIV-1 envelope (HIV-1 Env) glycoproteins are expressed on the cell surface, transforming latently infected cells into targets for HIV-1 Env-specific monoclonal antibodies (mAbs), which can engage immune effector cells to kill productively infected CD4(+) T cells and thus limit the spread of progeny virus...
December 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27707920/rationally-designed-immunogens-targeting-hiv-1-gp120-v1v2-induce-distinct-conformation-specific-antibody-responses-in-rabbits
#19
Xunqing Jiang, Max Totrov, Wei Li, Jared M Sampson, Constance Williams, Hong Lu, Xueling Wu, Shan Lu, Shixia Wang, Susan Zolla-Pazner, Xiang-Peng Kong
The V1V2 region of HIV-1 gp120 harbors a major vulnerable site targeted by a group of broadly neutralizing monoclonal antibodies (MAbs) such as PG9 through strand-strand recognition. However, this epitope region is structurally polymorphic as it can also form a helical conformation recognized by RV144 vaccine-induced MAb CH58. This structural polymorphism is a potential mechanism for masking the V1V2 vulnerable site. Designing immunogens that can induce conformation-specific antibody (Ab) responses may lead to vaccines targeting this vulnerable site...
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27667465/-upregulated-pd-1-on-cd8-t-cells-is-positively-correlated-with-activation-of-t-cells-during-hiv-1-infection
#20
Jian Xiao, Xian Liu, Xiaolei Yu, Yuan Dong, Xuqin Wang, Jing Leng, Rongge Yang, Ying Wang
Objective To investigate the expressions of programmed death-1 (PD-1), CD38, human leukocyte antigen DR (HLA-DR) and anligen KI-67(ki67) on CD8(+) T cells, and the correlation between PD-1/PD-L1 pathway and activation, immunodepletion during HIV-1 infection. Methods Peripheral blood mononuclear cells were isolated by density gradient centrifugation from 87 HIV-1 patients and 22 healthy controls. The expression levels of PD-1, CD38, HLA-DR and ki67 on CD8(+)T cells were detected by flow cytometry. Furthermore, we evaluated the production of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) in CD8(+) T cells by blocking PD-1/PD-L1 pathway in the presence of PD-L1 mAb...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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