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Targeting HIV Env immunogens to B cell follicles in non-human primates through immune complex or protein nanoparticle formulations

biorxiv. 2020; 
Jacob T. Martin, Christopher A. Cottrell, Aleksandar Antanasijevic, Diane G. Carnathan, Benjamin J. Cossette, Chiamaka A. Enemuo, Etse H. Gebru, Yury Choe, Federico Viviano, Talar Tokatlian, Kimberly M. Cirelli, George Ueda, Jeffrey Copps, Torben Schiffner, Sergey Menis, William R. Schief, Shane Crotty, Neil P. King, David Baker, Guido Silvestri, Andrew B. Ward, Darrell J. Irvine
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Cellular Analysis Nanoparticle components (BG505 SOSIP-T33_dn2A and T33_dn2B) were concentrated to ~1 mg/ml and equimolar amounts were combined and incubated for 24 hours at 4 °C, for nanoparticle assembly. Assembled nanoparticles were purified from the unassembled components using Sephacryl S-500 HR column using DPBS (Thermo Fisher Scientific) as the running buffer. ToxinSensorTM Single Test Kit (GenScript) was applied to verify that the endotoxin levels of the labeled nanoparticle were below 50 EU/kg per dose. Get A Quote

Abstract

Following immunization, high affinity antibody responses develop within germinal centers (GCs), specialized sites within follicles of the lymph node (LN) where B cells proliferate and undergo somatic hypermutation. Antigen availability within GCs is important, as B cells must acquire and present antigen to follicular helper T cells to drive this process. However, recombinant protein immunogens such as soluble HIV envelope (Env) trimers do not efficiently accumulate in follicles following traditional immunization. Here we demonstrate two strategies to concentrate HIV Env immunogens in follicles, via the formation of immune complexes (ICs) or by employing self-assembling protein nanoparticles for multivalent disp... More

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