Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 19 of 19 for “"CD4 binding site"”.
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Targeting the CD4 Binding Site of HIV
… locus in mice. 3BNC60 is a bNAb that targets the CD4 binding site (CD4bs) of HIV-1 and belongs to the IgHV1-2 class of broadly neutralizing CD4bs antibodies. In the first part of my thesis I will describe the evolution of the HIV-1 antibody response in GLVH and MuVH mice upon immunization. We …
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Engineering of HIV gp120 by yeast surface display for neutralizing antibody characterization and immunogen design
… pressure. Certain conserved epitopes, like the CD4 binding site, are required for viral fitness and antibodies against these epitopes are able to neutralize HIV from multiple clades. Passive immunization experiments suggest that eliciting such broadly reactive antibodies by vaccination may …
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HIV Specific B Cell Response in Patients With Broadly Neutralizing Serum Activity
… HIV we cloned 1078 antibodies from HIV envelope binding memory B cells from eight HIV infected patients with broadly neutralizing antibodies. We found that in these patients, the B cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity antibodies to the …
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HIV-1 Immune Escape and Neutralizing Antibodies : Solid Phase Proteoliposomes Containing HIV-1 Envelope Glycoproteins as Antigens and Immunogens and HIV-1 Core Envelope Glycoproteins Deficient in T-Helper Epitopes
… envelope glycoproteins gp120 and gp41 mediate binding and fusion of the virus to target cells. The envelope glycoproteins are exposed on the surface of the virus as trimeric spikes and are the major targets for neutralizing antibodies. The design of envelope glycoprotein-based subunit vaccines …
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Dissociating Siv Env and Cd4: Consequenes for Virus and Host
CD4 tropism is conserved among all primate lentiviruses and likely contributes to viral pathogenesis by targeting cells that are critical for the adaptive anti-viral immune responses. Although CD4-independent variants of HIV and SIV have been described that can utilize coreceptors CCR5 or CXCR4 in …
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Humanized Mouse with a Diverse Polyclonal B Cell Repertoire as a Model for Neutralizing Antibody Responses against EBV and HIV
… broadly neutralizing antibodies that target the CD4 binding site on HIV envelope. I utilized high-throughput sequencing to identify the presence of these rare potentially protective B cells in humanized mice and evaluated if an anti-idiotypic immunogen, designed to target genetically encoded …
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DESIGN AND DEVELOPMENT OF RNA-BASED DRUGS USING MOLECULAR DYNAMICS SIMULATIONS AND ARTIFICIAL INTELLIGENCE METHODS
… inhibition was pursued by targeting the LC3B RNA-binding motif using novel Peptide Nucleic Acids (PNAs) to disrupt cancer cell survival mechanisms. Second, XNA sequences were optimized to target the DNA-binding domain of the oncogenic protein HMGB1. Third, aptamers were designed to bind the …
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Development and Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1
… Envelope, often involving the highly conserved CD4-binding site on the HIV Envelope. In a case study of an HIV-1-infected individual we aimed to understand the emergence and evolution of the earliest cross-neutralizing antibody responses, and identified two distinct epitope specificities. …
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Mechanisms of CCR5 Agonist/Antagonist Inhibition of HIV-1 Entry and In Vitro Selection of Virus Resistant to Maraviroc
… studies presented here demonstrate competitive binding between the envelope glycoprotein and inhibitor for CCR5 is a major mechanism involved in sensitivity to PSC-RANTES. Although downregulation of coreceptor expression from the cell surface was instigated by PSC-RANTES binding, this effect was …
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The Development and Assessment of Immune Responses in Plasmid DNA, VSV-Vectored, and Virus-Like Particle HIV Vaccinations in Murine Models
… conformational changes: vaccines with or without CD4 mimetic interaction, to identify the best vaccine candidate. We also investigated the mechanisms by which these vaccines elicit humoral and cellular immune responses in mice by assessing antibody levels in sera and evaluating the phenotypes and …
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Design and characterization of novel immunogens for AIDS vaccine development and evaluation of a sample inference method for NGS Illumina amplicon data
… proximal external region (MPER) of gp41 and the CD4 binding site (CD4bs) of gp120 have become attractive targets for vaccine development because they contain highly conserved epitopes recognized by some of the broadest neutralizing antibodies. Here, we have designed and characterized multiple …
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The screening of neutralising antibodies against a resistant HIV-1 strain to identify novel epitopes
… to monoclonal antibodies (mAbs) b12 (anti-CD4-binding site), 2G12 (anti-V3/glycan), 2F5 and 4E10 (both anti-membrane proximal external region). Of note, the virus is resistant to the extremely broad and potent mAb VRC01 (anti-CD4-bs). QH343.A10 was also found to be resistant to …
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Characterisation of llama antibody fragments able to act as HIV-1 entry inhibitors
… the envelope spike to the main cellular receptor CD4, allowing interaction with a co-receptor and eventually fusion of viral and cellular membranes. Neutralising antibodies inhibit HIV-1 entry by targeting epitopes on the functional spike. HIV-1 has, however, evolved several ways to evade …
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Modulating the Antigenicity and Immunogenicity of HIV-1 Envelope by a Conserved N-Linked Glycan
… by glycans contributes to masking conserved sites that are targets for some broadly neutralizing antibodies (bNAbs). Previous work has shown that removal of a highly conserved potential N-linked glycan (PNLG) site at amino acid residue 197 (N7) on the surface antigen gp120 of HIV-1 envelope …
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Understanding the interplay between HIV-1 diversity, humoral immune responses and viral fitness
… in the HISIS cohort with responses targeting the CD4 binding site. While neutralizing antibodies are considered central for protection from infection, ADCC activity correlated with reduced risk of HIV-1 acquisition in the RV144 trial. There is limited understanding of the overlapping ADCC and …
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Characterisation of functional properties of Envelopes of highly neutralisation resistant HIV-1 isolates
… to the PGT121 (V3/glycan), 4E10 (MPER) and the CD4 binding site broadly neutralising antibodies VRC01 and 3BNC117; suggesting that the epitopes of these antibodies are important for driving resistance. Furthermore, we found no significant relationship between susceptibility to the entry …
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The impact of neutralizing antibody and ADCC responses on HIV-1 envelope evolution in early infection
… in one of these participants, which targeted the CD4- binding site, revealed three distinct escape pathways, of which two conferred resistance to ADCC, and confirmed that ADCC responses can directly drive viral evolution in vivo. Finally, we investigated the ADCC activity of eleven anti-HIV-1 …
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Generation and characterization of HIV-1 subtype C candidate vaccines that will induce high titre antibody responses to HIV-1 envelope glycoprotein
… plasminogen activator leader, the furin cleavage site with a glycine rich flexible linker, and to introduce an I559P mutation. DNA and modified vaccinia virus Ankara (MVA) vaccines were generated where Env was truncated to gp150, thereby retaining the transmembrane domain and a partial cytoplasmic …
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The Ontogeny of Vaccine-Induced HIV-1 Glycan-Reactive Antibodies
… antibodies (bnAbs). BnAbs target conserved sites on the HIV-1 Env glycoprotein trimer including the membrane proximal external region, the gp120-gp41 interface, the CD4 binding site, V1V2-loop plus glycans, and the V3 loop plus glycans. Passive infusion studies with broadly neutralizing …