作者: Klein, Florian ; Ensser, Armin ; Stahl-Hennig, Christiane ; Fraedrich, Kirsten ; Sauermann, Ulrike ; Tenbusch, Matthias ; Stab, Viktoria ; Richel, Elie ; Burton, Dennis R ; Überla, Klaus ; Tippler, Bettina

Neutralizing antibodies targeting HIV-1 Env have been shown to protect from systemic infection. To explore whether these antibodies can inhibit infection of the first cells, challenge viruses based on simian immunodeficiency virus (SIV) were developed that use HIV-1 Env for entry into target cells during the first replication cycle, but then switch to SIV Env usage. Antibodies binding to Env of HIV-1, but not SIV, block HIV-1 Env-mediated infection events after rectal exposure of non-human primates to the switching challenge virus. After natural exposure to HIV-1, such a reduction of the number of first infection events should be sufficient to provide sterilizing immunity in the strictest sense in most of the exposed individuals. Since blocking infection of the first cells avoids the formation of latently infected cells and reduces the risk of emergence of antibody-resistant mutants, it may be the best mode of protection.

2022-06-01·Cell Reports

B cells expressing IgM B cell receptors of HIV-1 neutralizing antibodies discriminate antigen affinities by sensing binding association rates

Article

作者: Saunders, Kevin ; Reth, Michael ; Watts, Brian ; Edwards, R J ; Schief, William R ; Ortiz, Yaneth ; Rountree, Wes ; Derking, Ronald ; Zhang, Jinsong ; Sanders, Rogier W ; Alam, S Munir ; Anasti, Kara ; Easterhoff, David ; Groschel, Bettina ; Kane, Advaiti Pai ; Hossain, Md Alamgir ; Cronin, Kenneth ; Verkoczy, Laurent

HIV-1 envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant [K_D]) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding K_D and whether B cells discriminate among proteins of similar affinities that bind with different kinetic rates. Here, we use a panel of Env proteins and Ramos B cell lines expressing immunoglobulin M (IgM) B cell receptors (BCRs) with specificity for CD4-binding-site broadly neutralizing antibodies to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall K_D but on sensing of association rate and a threshold antigen-BCR half-life.

2018-08-01·Analytical Biochemistry4区 · 生物学

Long term stability of a HIV-1 neutralizing monoclonal antibody using isothermal calorimetry

4区 · 生物学

Article

作者: Kueltzo, Lisa ; Schön, Arne ; Chaudhuri, Rajoshi ; Freire, Ernesto ; Cooper, Jonathan W ; Clarkson, Benjamin R

Different factors affect the long term stability of monoclonal antibodies, among them denaturation or partial denaturation that is often followed by aggregation. Isothermal calorimetry is capable of quantifying the kinetics of denaturation/aggregation of an antibody by measuring the heat that is released or absorbed by the process over a period of days or weeks, at temperatures below its denaturation temperature, T_m. The denaturation/aggregation kinetics of the anti-HIV monoclonal antibody VRC07-523LS was measured by isothermal calorimetry at different concentrations in four different formulation buffers. The measurements were performed at ten degrees below T_m, as determined by differential scanning calorimetry. The formation of aggregates was also followed by size exclusion chromatography at 5 °C, 25 °C and 40 °C over a period of 8-36 weeks. It was observed that the rates measured by isothermal calorimetry correlate quantitatively with those measured by size exclusion chromatography. Since isothermal calorimetry experiments are performed over a period of ten days, it can become a valuable tool for a fast prediction of the best formulations.

100 项与 HIV-1 neutralizing antibody(Duke University School of Medicine) 相关的药物交易

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