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nab hiv

Muzamil Ashraf Makhdoomi, Deepti Singh, Ambili Nair Pananghat, Rakesh Lodha, Sushil Kumar Kabra, Kalpana Luthra
Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been extensively tested against pesudoviruses of diverse strains. We generated and characterized HIV-1 primary isolates from antiretroviral naïve infected Indian children, and determined their susceptibility to known NAbs. All the 8 isolates belonged to subtype-C and were R5 tropic. Majority of these viruses were resistant to neutralization by NAbs, suggesting that the bnAbs, known to efficiently neutralize pseudoviruses (adult and pediatric) of different strains, are less effective against pediatric primary isolates...
September 16, 2016: Virology
P J Klasse, Celia C LaBranche, Thomas J Ketas, Gabriel Ozorowski, Albert Cupo, Pavel Pugach, Rajesh P Ringe, Michael Golabek, Marit J van Gils, Miklos Guttman, Kelly K Lee, Ian A Wilson, Salvatore T Butera, Andrew B Ward, David C Montefiori, Rogier W Sanders, John P Moore
We have investigated the immunogenicity in rabbits of native-like, soluble, recombinant SOSIP.664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 (HIV-1); specifically BG505 (clade A), B41 (clade B), CZA97 (clade C) and DU422 (clade C). The various trimers were delivered either simultaneously (as a mixture of clade A + B trimers) or sequentially over a 73-week period. Autologous, Tier-2 neutralizing antibody (NAb) responses were generated to the clade A and clade B trimers in the bivalent mixture...
September 2016: PLoS Pathogens
Laura E McCoy, Marit J van Gils, Gabriel Ozorowski, Terrence Messmer, Bryan Briney, James E Voss, Daniel W Kulp, Matthew S Macauley, Devin Sok, Matthias Pauthner, Sergey Menis, Christopher A Cottrell, Jonathan L Torres, Jessica Hsueh, William R Schief, Ian A Wilson, Andrew B Ward, Rogier W Sanders, Dennis R Burton
A major advance in the search for an HIV vaccine has been the development of a near-native Envelope trimer (BG505 SOSIP.664) that can induce robust autologous Tier 2 neutralization. Here, potently neutralizing monoclonal antibodies (nAbs) from rabbits immunized with BG505 SOSIP.664 are shown to recognize an immunodominant region of gp120 centered on residue 241. Residue 241 occupies a hole in the glycan defenses of the BG505 isolate, with fewer than 3% of global isolates lacking a glycan site at this position...
August 30, 2016: Cell Reports
Samantha Townsley, Zeinab Mohamed, Wenjin Guo, Jennifer McKenna, Brad Cleveland, Celia LaBranche, David Beaumont, Xiaoying Shen, Nicole L Yates, Abraham Pinter, Georgia D Tomaras, Guido Ferrari, David C Montefiori, Shiu-Lok Hu
UNLABELLED: Poxvirus prime-protein boost used in the RV144 trial remains the only immunization strategy shown to elicit a modest level of protection against HIV-1 acquisition in humans. Although neutralizing antibodies (NAb) were generated, they were against sensitive viruses, not the more resistant "tier 2" isolates that dominate circulating strains. Instead, risk reduction correlated with antibodies recognizing epitopes in the V1/V2 region of HIV-1 envelope glycoprotein (Env). Here, we examined whether tier 2 virus NAb and V1/V2-specific non-NAb could be elicited by a poxvirus prime-gp120 boost strategy in a rabbit model...
October 1, 2016: Journal of Virology
Tom L G M van den Kerkhof, Steven W de Taeye, Brigitte D Boeser-Nunnink, Dennis R Burton, Neeltje A Kootstra, Hanneke Schuitemaker, Rogier W Sanders, Marit J van Gils
BACKGROUND: Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design. RESULTS: Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection...
2016: Retrovirology
Yuta Hikichi, Masaru Yokoyama, Taichiro Takemura, Masayuki Fujino, Sei Kumakura, Yosuke Maeda, Naoki Yamamoto, Hironori Sato, Tetsuro Matano, Tsutomu Murakami
HIV-1 passage in cell culture in the presence of chemokine receptor antagonists can result in selection of viruses with env mutations that confer resistance to these inhibitors. In the present study, we examined the effect of HIV-1env mutations that confer resistance to CXCR4 antagonists on envelope (Env) sensitivity to neutralizing antibodies (NAbs). Serial passage of CXCR4-tropic HIV-1 NL4-3 in PM1/CCR5 cells under CXCR4 antagonists KRH-3955, AMD3100 and AMD070 yielded two KRH-3955-resistant, one AMD3100-resistant and one AMD070-resistant viruses...
September 2016: Journal of General Virology
Linling He, Natalia de Val, Charles D Morris, Nemil Vora, Therese C Thinnes, Leopold Kong, Parisa Azadnia, Devin Sok, Bin Zhou, Dennis R Burton, Ian A Wilson, David Nemazee, Andrew B Ward, Jiang Zhu
Structures of BG505 SOSIP.664 trimer in complex with broadly neutralizing antibodies (bNAbs) have revealed the critical role of trimeric context for immune recognition of HIV-1. Presentation of trimeric HIV-1 antigens on nanoparticles may thus provide promising vaccine candidates. Here we report the rational design, structural analysis and antigenic evaluation of HIV-1 trimer-presenting nanoparticles. We first demonstrate that both V1V2 and gp120 can be presented in native-like trimeric conformations on nanoparticles...
2016: Nature Communications
Cassandra A Simonich, Katherine L Williams, Hans P Verkerke, James A Williams, Ruth Nduati, Kelly K Lee, Julie Overbaugh
HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth...
June 30, 2016: Cell
Sumire Iseda, Naofumi Takahashi, Hugo Poplimont, Takushi Nomura, Sayuri Seki, Taku Nakane, Midori Nakamura, Shoi Shi, Hiroshi Ishii, Shota Furukawa, Shigeyoshi Harada, Taeko K Naruse, Akinori Kimura, Tetsuro Matano, Hiroyuki Yamamoto
UNLABELLED: Identifying human immunodeficiency virus type 1 (HIV-1) control mechanisms by neutralizing antibodies (NAbs) is critical for anti-HIV-1 strategies. Recent in vivo studies on animals infected with simian immunodeficiency virus (SIV) and related viruses have shown the efficacy of postinfection NAb passive immunization for viremia reduction, and one suggested mechanism is its occurrence through modulation of cellular immune responses. Here, we describe SIV control in macaques showing biphasic CD8(+) cytotoxic T lymphocyte (CTL) responses following acute-phase NAb passive immunization...
July 15, 2016: Journal of Virology
P J Klasse
Neutralizing antibodies (NAbs) can be both sufficient and necessary for protection against viral infections, although they sometimes act in concert with cellular immunity. Successful vaccines against viruses induce NAbs but vaccine candidates against some major viral pathogens, including HIV-1, have failed to induce potent and effective such responses. Theories of how antibodies neutralize virus infectivity have been formulated and experimentally tested since the 1930s; and controversies about the mechanistic and quantitative bases for neutralization have continually arisen...
2014: Advances in Biology
Marion Cornelissen, Zelda Euler, Tom L G M van den Kerkhof, Marit J van Gils, Brigitte D M Boeser-Nunnink, Neeltje A Kootstra, Fokla Zorgdrager, Hanneke Schuitemaker, Jan M Prins, Rogier W Sanders, Antoinette C van der Kuyl
The effect of serial HIV-1 infection on the development of the broadly neutralizing antibody (bNAb) response was studied in an individual, H01-10366, with a serial HIV-1 superinfection (SI), hence triple infection, and compared with the bNAb response in three superinfected as well as 11 monoinfected men who have had sex with men (MSM) from Amsterdam, the Netherlands. Neutralization assays measuring heterologous neutralizing antibody (NAb) titers on a panel of six representative viruses from different HIV-1 subtypes were performed on blood serum samples obtained ∼3 years after primary HIV infection (PHI) and longitudinally for H01-10366...
February 24, 2016: AIDS Research and Human Retroviruses
Steven W de Taeye, John P Moore, Rogier W Sanders
The identification of multiple broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer has facilitated its structural characterization and guided Env immunogen design. Several recent studies constitute progress in utilizing this knowledge for the development of an HIV-1 vaccine that induces bNAbs. Native-like Env trimers can induce autologous NAb responses against resistant (Tier-2) viruses in several animal models. Here we review recent studies aimed at addressing the challenge of driving the strong but narrowly focused NAb responses to Env trimers towards ones with much greater breadth...
March 2016: Trends in Immunology
Caitlin Milligan, Maxwel M Omenda, Vrasha Chohan, Katherine Odem-Davis, Barbra A Richardson, Ruth Nduati, Julie Overbaugh
UNLABELLED: Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission...
2016: MBio
Todd Bradley, Daniela Fera, Jinal Bhiman, Leila Eslamizar, Xiaozhi Lu, Kara Anasti, Ruijung Zhang, Laura L Sutherland, Richard M Scearce, Cindy M Bowman, Christina Stolarchuk, Krissey E Lloyd, Robert Parks, Amanda Eaton, Andrew Foulger, Xiaoyan Nie, Salim S Abdool Karim, Susan Barnett, Garnett Kelsoe, Thomas B Kepler, S Munir Alam, David C Montefiori, M Anthony Moody, Hua-Xin Liao, Lynn Morris, Sampa Santra, Stephen C Harrison, Barton F Haynes
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus...
January 5, 2016: Cell Reports
Cheng Cheng, Marie Pancera, Adam Bossert, Stephen D Schmidt, Rita E Chen, Xuejun Chen, Aliaksandr Druz, Sandeep Narpala, Nicole A Doria-Rose, Adrian B McDermott, Peter D Kwong, John R Mascola
UNLABELLED: The HIV-1 envelope trimer (Env) is the target of broadly neutralizing antibodies and is being explored as a vaccine candidate to elicit protective antibodies. One of the most promising antigenic and structural mimics of HIV-1 Env is the SOSIP.664-stabilized soluble trimer from the clade A strain BG505, which is preferentially recognized by broadly neutralizing antibodies. Trimer immunization elicits high-titer neutralization of the autologous tier 2 BG505 strain; however, breadth is limited, and substantial interest has focused on understanding and improving trimer immunogenicity...
March 2016: Journal of Virology
Juan Zhao, Jianhui Nie, Yanmei Jiao, Lan Li, Tong Zhang, Qiang Liu, Weijin Huang, Hao Wu, Youchun Wang
Delineating the course of NAb (neutralizing antibody) development in natural infection may provide clues for NAb-targeted HIV-1 vaccine design. Two subjects, A (non-neutralizer) and E (neutralizer), were chosen from 75 HIV-1 positive subjects of a MSM (men who have sex with men) cohort to investigate the key events of virus evolution in the development course of neutralizing antibodies. Pseudovirus quasispecies (at least 10 strains) were generated for each time points of the infection course. The diversity and divergence of the env quasispecies per time point for subject E were significantly higher than those for subject A (p<0...
March 2016: Infection, Genetics and Evolution
Steven W de Taeye, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L G M van den Kerkhof, Judith A Burger, Laura K Pritchard, Pavel Pugach, Anila Yasmeen, Jordan Crampton, Joyce Hu, Ilja Bontjer, Jonathan L Torres, Heather Arendt, Joanne DeStefano, Wayne C Koff, Hanneke Schuitemaker, Dirk Eggink, Ben Berkhout, Hansi Dean, Celia LaBranche, Shane Crotty, Max Crispin, David C Montefiori, P J Klasse, Kelly K Lee, John P Moore, Ian A Wilson, Andrew B Ward, Rogier W Sanders
The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes...
December 17, 2015: Cell
Dan Li, Zheng Wang, Li Ren, Jing Zhang, Guangda Feng, Kunxue Hong, Yanling Hao, Zhi Qi, Hua Liang, Yiming Shao
Broadly neutralizing antibodies (NAbs) against the CD4 binding site of HIV gp120 (CD4bs) have provided important information for vaccine design. In this study, we combined deep sequencing and single memory B cell sorting to isolate CD4bs-directed NAbs from a Chinese HIV-1-infected elite neutralizer. We first performed 454 pyrosequencing to capture the IGHV1, IGKV, and IGLV germline gene families. IGHV1-2*02, the heavy chain germline V gene (VH) of the CD4bs-directed bNAb VRC01, was found to have a relatively low somatic mutation rate...
April 2016: Archives of Virology
Lin Liu, David Nardo, Eric Li, Gary P Wang
OBJECTIVES: CD4 T-cell depletion from HIV infection leads to a global decline in anti-hepatitis C virus (HCV) envelope neutralizing antibody (nAb) response, which may play a role in accelerating liver fibrosis. An increase in anti-HCV nAb titers has been reported during antiretroviral therapy (ART) but its impact on HCV remains poorly understood. The objective of this study is to determine the effects of ART on long-term HCV evolution. DESIGN AND METHODS: We examined HCV quasispecies structure and long-term evolution in HIV/HCV coinfected patients with ART-induced CD4 T-cell recovery, and compared with patients with CD4 T-cell depletion from delayed ART...
March 13, 2016: AIDS
Yanille M Scott, Seo Young Park, Charlene S Dezzutti
Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through mucosal tissue, thus reducing the incidence of HIV infection...
February 2016: Antimicrobial Agents and Chemotherapy
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