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HIV neutralizing antibody

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https://www.readbyqxmd.com/read/28429756/a-non-canonical-binding-interface-in-the-crystal-structure-of-hiv-1-gp120-core-in-complex-with-cd4
#1
Liang-Wei Duan, Hui Zhang, Meng-Ting Zhao, Ji-Xue Sun, Wen-Li Chen, Jian-Ping Lin, Xin-Qi Liu
Numerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427948/comprehensive-characterization-of-humoral-correlates-of-human-immunodeficiency-virus-1-superinfection-acquisition-in-high-risk-kenyan-women
#2
Keshet Ronen, Adam S Dingens, Susan M Graham, Walter Jaoko, Kishor Mandaliya, R Scott McClelland, Julie Overbaugh
HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design...
April 7, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28425451/ifn%C3%AE-protects-neurons-from-damage-in-a-murine-model-of-hiv-1-associated-brain-injury
#3
Victoria E Thaney, Alan M O'Neill, Melanie M Hoefer, Ricky Maung, Ana B Sanchez, Marcus Kaul
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424455/flow-virometry-analysis-of-envelope-glycoprotein-conformations-on-individual-hiv-virions
#4
Anush Arakelyan, Wendy Fitzgerald, Deborah F King, Paul Rogers, Hannah M Cheeseman, Jean-Charles Grivel, Robin J Shattock, Leonid Margolis
HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus-cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10-14 Envs, and therefore a defective Env may not necessarily render a HIV virion non-infectious, since other Env on the same virion may still be functional. Alternatively, it is possible that on a given virion either all the spikes are defective or all are functional...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423342/a-broadly-neutralizing-antibody-targets-the-dynamic-hiv-envelope-trimer-apex-via-a-long-rigidified-and-anionic-%C3%AE-hairpin-structure
#5
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A Cottrell, Travis Nieusma, Claudia Blattner, James C Paulson, Per Johan Klasse, Ian A Wilson, Dennis R Burton, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422793/engineering-antibody-like-inhibitors-to-prevent-and-treat-hiv-1-infection
#6
Matthew R Gardner, Michael Farzan
PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs)...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422792/progress-in-hiv-1-antibody-research-using-humanized-mice
#7
Henning Gruell, Florian Klein
PURPOSE OF REVIEW: Recent discoveries of highly potent broadly HIV-1 neutralizing antibodies provide new opportunities to successfully prevent, treat, and potentially cure HIV-1 infection. To test their activity in vivo, humanized mice have been shown to be a powerful model and were used to investigate antibody-mediated prevention and therapy approaches. In this review, we will summarize recent findings in humanized mice that have informed on the potential use of broadly neutralizing antibodies targeting HIV-1 in humans...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422791/intrastructural-help-improving-the-hiv-1-envelope-antibody-response-induced-by-virus-like-particle-vaccines
#8
Vladimir Temchura, Klaus Überla
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422790/particle-based-delivery-of-the-hiv-envelope-protein
#9
Benedikt Asbach, Ralf Wagner
PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422789/antigp41-membrane-proximal-external-region-antibodies-and-the-art-of-using-the-membrane-for-neutralization
#10
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/28422788/stabilized-hiv-1-envelope-glycoprotein-trimers-for-vaccine-use
#11
Max Medina-Ramírez, Rogier W Sanders, Quentin J Sattentau
PURPOSE OF REVIEW: To provide an update on the latest developments in the field of HIV-1 antibody-based soluble envelope glycoprotein (Env) trimer design for vaccine use. RECENT FINDINGS: The development of soluble native-like HIV-1 Env trimer immunogens has moved the field of antibody-based vaccine design forward dramatically over the past few years with refinement of various stabilizing approaches. However, despite this progress, significant challenges remain...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422787/how-hiv-1-entry-mechanism-and-broadly-neutralizing-antibodies-guide-structure-based-vaccine-design
#12
Marie Pancera, Anita Changela, Peter D Kwong
PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies (bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1 entry mechanism is guiding the structure-based design of vaccine immunogens and immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected donors has led to an unprecedented understanding of the sites of vulnerability that these antibodies target on the HIV-1 envelope (Env) as well as of the immunological pathways that these antibody lineages follow to develop broad and potent neutralization...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422786/antibody-mediated-immune-exclusion-of-hiv
#13
Ruth M Ruprecht, Samir K Lakhashe
PURPOSE OF REVIEW: Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. RECENT FINDINGS: Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422785/role-of-nonneutralizing-antibodies-in-vaccines-and-or-hiv-infected-individuals
#14
Luzia Mayr, Bin Su, Christiane Moog
PURPOSE OF REVIEW: Increased body of evidence gathered over time indicate that antibodies are capable of many inhibitory mechanisms, virus neutralization being just one of them. Nonneutralizing antibodyactivities interfering with HIV replication can also lead to a decrease in viral load and even in-vivo protection. RECENT FINDINGS: It was previously believed that neutralizing antibodies can achieve sterilizing protection mainly by using their neutralization capacities against the infecting virus directly at the portal of virus entry...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422784/b-cell-abnormalities-and-impact-on-antibody-response-in-hiv-infection
#15
Alessandra Noto, Giuseppe Pantaleo
PURPOSE OF REVIEW: The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection. RECENT FINDINGS: Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env)...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422783/lessons-learned-from-humoral-responses-of-hiv-patients
#16
Laura E McCoy, Áine McKnight
PURPOSE OF REVIEW: Since 2009 many broadly neutralizing antibodies against HIV have been identified, yet there is still no vaccine capable of inducing such antibodies in humans. This review considers the early observations of HIV sera neutralization in light of more recent studies and highlights areas for future research. RECENT FINDINGS: Large clinical cohort studies using standardized neutralization assays and pseudoviruses derived from primary isolates have shown that 10-30% of HIV infections result in some level of serum neutralization breadth...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28416548/pharmacokinetics-and-preliminary-safety-of-pod-intravaginal-rings-delivering-the-monoclonal-antibody-vrc01-n-for-hiv-prophylaxis-in-a-macaque-model
#17
Chunxia Zhao, Manjula Gunawardana, Francois Villinger, Marc M Baum, Mariana Remedios-Chan, Thomas R Moench, Larry Zeitlin, Kevin J Whaley, Ognian Bohorov, Thomas J Smith, Deborah J Anderson, John A Moss
The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known HIV-1 isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other under-developed regions may be limited by the high cost and limited manufacturing capacity of conventionally produced antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01-N over a range of release rates have been developed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28414420/systematic-synthesis-and-binding-study-of-hiv-v3-glycopeptides-reveal-the-fine-epitopes-of-several-broadly-neutralizing-antibodies
#18
Jared Orwenyo, Hui Cai, John Giddens, Mohammed N Amin, Christian Toonstra, Lai-Xi Wang
A class of new glycan-reactive broadly neutralizing antibodies represented by PGT121, 10-1074 and PGT128 has recently been discovered that target specific N-glycans and peptide region around the V3 domain. However, the glycan specificity and fine epitopes of these bNAbs remain to be further defined. We report here a systematic chemoenzymatic synthesis of homogeneous V3 glycopeptides derived from HIV-1 JR-FL strain carrying defined N-glycans at N332, N301 and N295 sites. Antibody binding studies revealed that both the nature and site of glycosylation in the context of the V3 domain were critical for high-affinity binding...
April 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28413022/humanized-immunoglobulin-mice-models-for-hiv-vaccine-testing-and-studying-the-broadly-neutralizing-antibody-problem
#19
Laurent Verkoczy
A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broadly neutralizing antibody (bnAb) responses. A major technical hurdle toward achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past 6 years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell tolerance mechanisms limiting bnAb production and evaluation of strategies to circumvent such processes...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28404572/an-hiv-envelope-gp120-fc-fusion-protein-elicits-effector-antibody-responses-in-rhesus-macaques
#20
Zhanna Shubin, Weizhong Li, Bhawna Poonia, Guido Ferrari, Celia LaBranche, David Montefiori, Xiaoping Zhu, C David Pauza
A goal for HIV prevention programs is to develop safe and effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization or glycosylation of gp120 to activate appropriate germline B cells and mimic the subsequent maturation pathways seen in infected individuals...
April 12, 2017: Clinical and Vaccine Immunology: CVI
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